A depressant, or central depressant, is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

that lowers

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

levels, which is to depress or reduce

arousal Arousal is the physiological and psychological state of being awoken or of sense organs stimulated to a point of perception. It involves activation of the ascending reticular activating system (ARAS) in the brain, which mediates wakefulness, th ...

or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the level of arousal when taken.

Stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

s or "uppers" increase mental or physical function, hence the opposite

drug class A drug class is a set of medications and other compounds that have a similar chemical structures, the same mechanism of action (i.e. binding to the same biological target), a related mode of action, and/or are used to treat the same disease. In ...

of depressants is stimulants, not

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s. Depressants are widely used throughout the world as

prescription medicine A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...

s and as illicit substances. Alcohol is a very prominent depressant. Alcohol can be and is more likely to be a large problem among teenagers and young adults. When depressants are used, effects often include

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

anxiolysis An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

pain relief Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professional ...

, sedation or

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

, and

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

memory impairment Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...

, as well as in some instances, euphoria,

dissociation Dissociation, in the wide sense of the word, is an act of disuniting or separating a complex object into parts. Dissociation may also refer to: * Dissociation (chemistry), general process in which molecules or ionic compounds (complexes, or salts ...

muscle relaxation Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscl ...

, lowered

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...

, respiratory depression, and

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

effects. Depressants also act to produce

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

Cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...

may sometimes be considered a depressant due to one of its components,

cannabidiol Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. , clinical research on CBD incl ...

. The latter is known to treat insomnia, anxiety and muscle spasms similar to other depressive drugs. However,

tetrahydrocannabinol Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...

, another component, may slow brain function to a small degree while reducing reaction to stimuli, it is generally considered to be a stimulant and main psychoactive agent to sometimes cause anxiety,

panic Panic is a sudden sensation of fear, which is so strong as to dominate or prevent reason and logical thinking, replacing it with overwhelming feelings of anxiety and frantic agitation consistent with an animalistic fight-or-flight reactio ...

and

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

instead. Other depressants can include drugs like

Xanax Alprazolam, sold under the brand name Xanax, among others, is a fast-acting, potent tranquilizer of medium duration in the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It is most commonly ...

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

) and a number of opioids.

Gabapentinoid Gabapentinoids, also known as α2δ ligands, are a class of drugs that are derivatives of the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) (i.e., GABA analogues) which block α2δ subunit-containing voltage-dependent calcium ch ...

s like

gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabeti ...

and

baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

are depressants and have anticonvulsant and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...

effects. Most anticonvulsants like Lamotrigine and

Phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...

are depressants. Carbamates (

Felbamate Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant used in the treatment of epilepsy. It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associa ...

Carisoprodol) are depressants that are similar to

barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as we ...

s. Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA, and inhibition of

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonis ...

monoaminergic Monoaminergic means "working on monoamine neurotransmitters", which include serotonin, dopamine, norepinephrine, epinephrine, and histamine. A monoaminergic, or monoaminergic drug, is a chemical, which functions to directly modulate the ser ...

activity. Other examples are chemicals that modify the electrical signaling inside the body, the most prominent of these being

bromide A bromide ion is the negatively charged form (Br−) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retardant ...

s and

channel blocker A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, suc ...

Indications

Depressants are used medicinally to relieve the following symptoms: *

Anxiety disorders Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

such as: ** Generalized anxiety **

Social anxiety Social anxiety is the anxiety and fear specifically linked to being in social settings (i.e., interacting with others). Some categories of disorders associated with social anxiety include anxiety disorders, mood disorders, autism spectrum disord ...

Panic attack Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...

s *

Insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

Obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and/or feels the need to perform certain routines repeatedly to the extent where it induces distress or impairs general ...

Seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

s * Convulsions * Depression * Pain

Types

Alcohol

An alcoholic beverage is a drink that contains alcohol (also known formally as

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

), an

anesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...

that has been used as a

psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...

for several

millennia A millennium (plural millennia or millenniums) is a period of one thousand years, sometimes called a kiloannum (ka), or kiloyear (ky). Normally, the word is used specifically for periods of a thousand years that begin at the starting point (ini ...

. Ethanol is the oldest

recreational drug Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...

still used by humans. Ethanol can cause

alcohol intoxication Alcohol intoxication, also known as alcohol poisoning, commonly described as drunkenness or inebriation, is the negative behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main p ...

when consumed. Alcoholic beverages are divided into three general classes for taxation and regulation of production:

beer Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from ce ...

wine Wine is an alcoholic drink typically made from fermented grapes. Yeast consumes the sugar in the grapes and converts it to ethanol and carbon dioxide, releasing heat in the process. Different varieties of grapes and strains of yeasts are m ...

s, and

spirits Spirit or spirits may refer to: Liquor and other volatile liquids * Spirits, a.k.a. liquor, distilled alcoholic drinks * Spirit or tincture, an extract of plant or animal material dissolved in ethanol * Volatile (especially flammable) liquids, ...

(distilled beverages). They are legally consumed in most countries around the world. More than 100 countries have laws regulating their production, sale, and consumption. The most common way to measure intoxication for legal or medical purposes is through

blood alcohol content Blood alcohol content (BAC), also called blood alcohol concentration or blood alcohol level, is a measurement of alcohol intoxication used for legal or medical purposes; it is expressed as mass of alcohol per volume or mass of blood. For exampl ...

(also called blood alcohol concentration or blood alcohol level). It is usually expressed as a

percentage In mathematics, a percentage (from la, per centum, "by a hundred") is a number or ratio expressed as a fraction of 100. It is often denoted using the percent sign, "%", although the abbreviations "pct.", "pct" and sometimes "pc" are also us ...

of alcohol in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

in units of mass of alcohol per volume of blood, or mass of alcohol per mass of blood, depending on the country. For instance, in North America a blood alcohol content of "0.10" or more correctly 0.10 g/dL means that there are 0.10 g of alcohol for every dL of blood (i.e., mass per volume is used there).

Barbiturates

Barbiturates are effective in relieving the conditions that they are designed to address (insomnia, seizures). They are also commonly used for unapproved purposes, are physically addictive, and have serious potential for overdose. In the late 1950s, when many thought that the social cost of barbiturates was beginning to outweigh the medical benefits, a serious search began for a replacement drug. Most people still using barbiturates today do so in the prevention of seizures or in mild form for relief from the symptoms of

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

Benzodiazepines

A benzodiazepine (sometimes colloquially "benzo"; often abbreviated "BZD") is a

whose core chemical structure is the fusion of a

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...

ring and a

diazepine Diazepine is a seven-membered heterocyclic compound with two nitrogen atoms (e.g., in ring positions 1 and 2). Types include: * 1,2-diazepine * 1,3-diazepine * 1,4-diazepine ** Benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes cal ...

ring. The first such drug,

chlordiazepoxide Chlordiazepoxide, trade name Librium among others, is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol and other drugs. Chlordiazepoxide has a medium t ...

(Librium), was discovered accidentally by

Leo Sternbach Leo Sternbach (May 7, 1908 – September 28, 2005) was a Polish American chemist who is credited with first synthesizing benzodiazepines, the main class of tranquilizers. Background and family Sternbach was born on May 7, 1908, in Opatija, K ...

in 1955, and made available in 1960 by

Hoffmann–La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

, which has also marketed the benzodiazepine

diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...

(Valium) since 1963. Benzodiazepines enhance the effect of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

gamma-aminobutyric acid (GABA) at the GABA_A receptor, resulting in

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

( sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and

muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeu ...

properties; also seen in the applied pharmacology of high doses of many shorter-acting benzodiazepines are

amnesic Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...

dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

actions. These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures,

muscle spasms A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...

alcohol withdrawal Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. M ...

and as a

premedication Premedication is using medication before some other therapy (usually surgery or chemotherapy) to prepare for that forthcoming therapy. Typical examples include premedicating with a sedative or analgesic before surgery; using prophylactic (prevent ...

for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety. In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and

paradoxical effect A paradoxical reaction (or paradoxical effect) is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication. Parado ...

s such as aggression or behavioral

disinhibition In psychology, disinhibition is a lack of restraint manifested in disregard of social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive, and perceptual aspects with signs and sympto ...

occasionally occur. A minority react reverse and contrary to what would normally be expected. For example, a state of panic may worsen considerably following intake of a benzodiazepine. Long-term use is controversial due to concerns about adverse psychological and physical effects, increased questioning of effectiveness, and, because benzodiazepines are prone to cause tolerance,

physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...

, and, upon cessation of use after long-term use,

benzodiazepine withdrawal syndrome Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a p ...

. Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The elderly are at an increased risk of experiencing both short- and long-term

adverse effects An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

. There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major

teratogens Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related ...

, uncertainty remains as to whether they cause

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...

in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn. Benzodiazepines can be taken in

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

s and can cause dangerous deep unconsciousness. However, they are much less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken; however, when combined with other

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

depressants such as

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

and

opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonis ...

s, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other addictive drugs. In addition, all benzodiazepines are listed in Beers List, which is significant in clinical practice.

Cannabis

is often considered either in its own unique category or as a mild

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...

. The chemical compound tetrahydrocannabinol (THC), which is found in cannabis, has many depressant effects such as

, sedation, decreased

alertness Alertness is the state of active attention by high sensory awareness such as being watchful and prompt to meet danger or emergency, or being quick to perceive and act. It is related for psychology . A lack of alertness is a symptom of a ...

, and less tiredness. Contrary to the previous statement, activation of the CB1 receptor by

cannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

causes an inhibition of GABA, the exact opposite of what central nervous system depressants do.

Carbamates

Carbamates are a class of depressants or "

tranquilizer A tranquilizer is a drug that is designed for the treatment of anxiety, fear, tension, agitation, and disturbances of the mind, specifically to reduce states of anxiety and tension. Etymology Tranquilizer, as a term, was first used by F.F. Yonk ...

s" that are synthesized from

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...

. Carbamates have

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...

, and

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

effects. It has other uses like muscle tremors, agitation, and

. It's muscle relaxant effects are useful for strains,

sprain A sprain, also known as a torn ligament, is an acute soft tissue injury of the ligaments within a joint, often caused by a sudden movement abruptly forcing the joint to exceed its functional range of motion. Ligaments are tough, inelastic fibers ...

s, and muscle injuries together with rest, physical therapy, and other measures. The effects, synthesis and mechanism of action of Carbamates are very similar to

s. There are many different types of Carbamates, some only produce anxiolytic effects and hypnotic effects while some only have anticonvulsant effects.

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of Carbamates include

drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, diarreha,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

flatulence Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed environm ...

, liver failure, poor coordination,

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

abuse Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...

weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

nervousness Nervous may refer to: * nervousness * Nervous system, a network of cells in an animal's body that coordinates movement and the senses ** Nervous tissue, the cells of the nervous system that work in aggregate to transmit signals Music * "Nervous" ...

, euphoria, overstimulation and dependence. Uncommon but potentially severe adverse reactions include hyper sensivity reactions including

Stevens Johnson syndrome Stevens may refer to: People * Stevens (surname), including a list of people with the surname Given name * Stevens Baker (1791–1868), farmer and member of the Legislative Assembly of Lower Canada * Stevens T. Mason (1811–1843), territorial g ...

, embryo-fetal toxicity, stupor, and

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

. Carbamates are fatal in

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

, which is why a lot of them have been replaced with

s. It is not recommended to use most Carbamates like Carisoprodol for a long time as

physical Physical may refer to: *Physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally co ...

and

psychological dependence Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exp ...

does occur.

Meprobamate Meprobamate—marketed as Miltown by Wallace Laboratories and Equanil by Wyeth, among others—is a carbamate derivative used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the be ...

which metabolizes to '' Carisoprodol'' was launched in 1955. It quickly become the first blockbuster psychotropic drug in America becoming popular in Hollywood and gaining fame for its seemingly miraculous effects. It has since been marketed under more than 100 trade names, from Amepromat through Quivet to Zirpon. Carisoprodol, which is still used today mainly for it's muscle relaxant effects has high abuse potential. It's mechanism of action is very similar to

methaqualone Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude ( ) and Sopor among others, which contained 300 mg of methaqualone, and sold as a combination drug under the brand name Mandrax, which contained 250 mg met ...

and

s. Carsidoprodol allosterically modulates and directly activates the human α1β2γ2 GABAAR ( GABA_A) in the

in a barbiturate-like manner. This causes

chloride channel Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Severa ...

s to open, allowing

chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...

to flood into the neuron, slowing down communication betwen neurons; thus slowing down the

nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...

. Unlike benzodiazpines which increase the frequency of the chloride channel opening, Carisoprodol increase the duration of channel opening when GABA is bound. GABA is the main

inhibitory An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...

in the

, which causes its depressant effects. Carbamates are fatal in overdose. Symptoms are similar to a

barbiturate overdose Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe ( respiratory depression). Complica ...

. Symptoms typically include difficulty thinking, poor coordination, decreased

level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousn ...

, and a decreased effort to breathe ( respiratory depression). An

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

is more likely to be fatal when it is mixed with another depressant that suppresses breathing. Death occurs this is typically due to a lack of breathing. Physical and psychological dependence does happen with long term use of Carbamates; particularly Carisoprodol. Today Carisoprodol is only used short term for muscle pain, particularly back pain. Discontuation after long term use could be very intense and even possibly fatal. Withdrawal can resemble

, or benzodiazepine withdrawal, as they all have a similar mechanism of action. Discontinuation symptoms include,

confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

disorientation Orientation is a function of the mind involving awareness of three dimensions: time, Location (geography), place and person. Problems with orientation lead to ''dis''orientation, and can be due to various conditions, from delirium to Substance int ...

delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...

hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...

s ( auditory &

visual The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight (the ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

decreased appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

psychomotor agitation Psychomotor agitation is a symptom in various disorders and health conditions. It is characterized by unintentional and purposeless motions and restlessness, often but not always accompanied by emotional distress. Typical manifestations include ...

, pressured speech,

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s which could be fatal. Carbamates we're popular in the 1950's along with barbiturates. Although they have been slowly phased out; mainly due to the overdose and dependence risks, new derivates still exist. Felbamate is an anticonvulsant that was approved in 1993 that is commonly used today. It is a GABA_A positive allosteric modulator and blocks the

NR2B Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the ''GRIN2B'' gene. NMDA receptors ''N''-methyl-D-aspartate (NMDA) receptors are ...

subunit of the

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...

. Some carbamates block

sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...

s. Phenprobamate was used as an anxiolytic and is still sometimes used in Europe for

general anesthesia General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...

and for treating muscle cramps and spasticity.

Methocarbamol Methocarbamol, sold under the brand name Robaxin among others, is a medication used for short-term musculoskeletal pain. It may be used together with rest, physical therapy, and pain medication. It is less preferred in low back pain. It has l ...

is a popular drug that is commonly known as Robaxin, that is

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

in some countries.. It is a carbamate with muscle relaxant effects.

Tetrabamate Tetrabamate (Atrium, G Tril, Sevrium) is a combination drug formulation of febarbamate, difebarbamate, and phenobarbital which was marketed in France and Spain and was used to treat anxiety and alcohol withdrawal-associated muscle tremors, ag ...

; a is a controversial drug which is a combination of

febarbamate Febarbamate ( INN; Solium, Tymium), also known as phenobamate, is an anxiolytic and tranquilizer of the barbiturate and carbamate families which is used in Europe by itself and as part of a combination drug formulation called tetrabamate. See a ...

, difebarbamate, and

phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...

which is marketed in Europe was largely but not completely discontinued. April 4, 1997 after over 30 years of use due to reports of

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

and

acute liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...

. The decision to restrict the use of the drug had been long-awaited. Carisoprodol; known as, "Soma" is still commonly used today for it's muscle relaxant effects. It is also very commonly abused around the world. It is a Schedule IV substance in the United States. Famous martial artist and actor

Bruce Lee Bruce Lee (; born Lee Jun-fan, ; November 27, 1940 – July 20, 1973) was a Hong Kong and American martial artist and actor. He was the founder of Jeet Kune Do, a hybrid martial arts philosophy drawing from different combat disciplines that ...

died due to an

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

to meprobamate. Approved * Carisoprodol/

Tybamate Tybamate (INN; Solacen, Tybatran, Effisax) is an anxiolytic of the carbamate family. It is a prodrug for meprobamate in the same way as the better known drug carisoprodol. It has liver enzyme inducing effects similar to those of phenobarbital ...

(Soma/Miltown, Solacen) (muscle relaxant, anxiolytic, tranquilizer) * Difebarbamate (Atrium, Sevrium) (tranquilizer) *

Emylcamate Emylcamate (marketed as Striatran by Merck) is an anxiolytic and muscle relaxant. It was patented in the US in 1961 (US Patent 2,972,564) and advertised for the treatment of anxiety and tension. It was claimed to be superior to meprobamate Me ...

(Striatran) (anxiolytic and muscle relaxant) * Ethinamate (Valamin, Valmid) (sedative-hypnotic) *

Febarbamate Febarbamate ( INN; Solium, Tymium), also known as phenobamate, is an anxiolytic and tranquilizer of the barbiturate and carbamate families which is used in Europe by itself and as part of a combination drug formulation called tetrabamate. See a ...

/ Phenobamate (Solium, Tymium) (anxiolytic and tranquilizer) *

(Felbatol) (anticonvulsant) *

Hexapropymate Hexapropymate is a hypnotic/ sedative. It has effects similar to those of barbiturates and was used in the 1970s-1980s in the treatment of insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sl ...

(Merinax) (hypnotic-sedative) *

Mebutamate Mebutamate (Capla, Dormate) is an anxiolytic and sedative drug with antihypertensive effects of the carbamate class. It has effects comparable to those of barbiturates such as secobarbital, but is only around 1/3 the potency of secobarbital as ...

(Capla, Dormate) (anxiolytic, sedative, antihypertensive) *

Phenprobamate Phenprobamate (Gamaquil, Isotonil) is a centrally acting skeletal muscle relaxant, with additional sedative and anticonvulsant effects. Overdose is similar to barbiturates. Its mechanism of action is probably similar to meprobamate. Phenproba ...

(Gamaquil, Isotonil) (muscle relaxant, sedative, anxiolytic, anticonvulsant, anesthesia) *

Procymate Procymate (Equipax) is a carbamate derivative which is a sedative and anxiolytic drug. It was previously manufactured and marketed in Belgium. The usual dose for adults is 800 to 1200 mg per day. Procymate shares a similar structure and mechanism ...

(Equipax) (sedative, anxiolytic) *

Styramate Styramate is a muscle relaxant and anticonvulsant drug. At therapeutic doses, it does not produce significant sedative effects. See also * Carisbamate Carisbamate (YKP 509, proposed trade name Comfyde) is an experimental anticonvulsant drug ...

(Sinaxamol) (muscle relaxant, anticonvulsant) *

(

, difebarbamate,

) (Atrium, G Tril, Sevrium) (anxiety, alcohol withdrawal, muscle tremors, agitation, depression) ''Although a drug may be approved, it does not necessarily mean it is still used today.'' Not approved * Carisbamate (anticonvulsant) *

Clocental Clocental (dolcental) is a carbamate-derived sedative hypnotic. It can be prepared by the ethynylation of cyclohexanone followed by reaction with allophanyl chloride. See also * 1-Ethynylcyclohexanol 1-Ethynylcyclohexanol (ECX) is an alk ...

(hypnotic) * Cyclarbamate (muscle relaxant and tranquilizer) * Lorbamate (muscle relaxant and tranquilizer) *

Nisobamate Nisobamate (INN; W-1015) is a tranquilizer of the carbamate family which was never marketed. See also * Meprobamate Meprobamate—marketed as Miltown by Wallace Laboratories and Equanil by Wyeth, among others—is a carbamate derivative ...

(tranquilizer) *

Pentabamate Pentabamate (S-109) is a tranquilizer A tranquilizer is a drug that is designed for the treatment of anxiety, fear, tension, agitation, and disturbances of the mind, specifically to reduce states of anxiety and tension. Etymology Tranquilize ...

(tranquilizer)

Gabapentinoids

s are a unique and relatively novel class of depressants that selectively

bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative ...

to the auxiliary α₂δ subunit (

CACNA2D1 Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the ''CACNA2D1'' gene. This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. ...

) and ( CACNA2D2), site of certain VDCCs, and thereby act as inhibitors of α₂δ subunit-containing

Voltage-gated calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabi ...

s. α₂δ is nicknamed the "Gabapentin receptor". At

physiologic Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

or resting

membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...

, VDCCs are normally closed. They are activated (opened) at depolarized

s and this is the source of the "

voltage-gated Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins ...

epithet An epithet (, ), also byname, is a descriptive term (word or phrase) known for accompanying or occurring in place of a name and having entered common usage. It has various shades of meaning when applied to seemingly real or fictitious people, di ...

. Gabapentinoids bind to the α1 and α2 sites of the α₂δ subunit family. Gabapentin is the

prototypical A prototype is an early sample, model, or release of a product built to test a concept or process. It is a term used in a variety of contexts, including semantics, design, electronics, and Software prototyping, software programming. A prototyp ...

gabapentinoid. The α₂δ is found on

L-type calcium channel The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This c ...

N-type calcium channel N-type calcium channels also called Cav2.2 channels are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the prima ...

s, P/Q-type calcium channels, and

R-type calcium channel The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties. This α1 subunit is al ...

s throughout the central and

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

s. α₂δ is located on presynaptic neurons and affects

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables e ...

trafficking and kinetics, initiates

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

signaling cascades,

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

and promotes

excitatory In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...

synaptogenesis Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenes ...

through

thrombospondin 1 Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the ''THBS1'' gene. Thrombospondin 1 is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell an ...

. Gabapentinoids are not direct

s, instead they disrupt the regulatory function of α₂δ and its interactions with other proteins. Most of the effects of gabapentinoids are mediated by the high voltage activated N and P/Q-type calcium channels. P/Q-type calcium channels are mainly found in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

( Purkinje neurons) which made be responsible for the

ataxic Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

adverse effect of gabapentinoids, while N-type calcium channels are located throughout the central and peripheral nervous systems.

s are mainly responsible for the

effects of gabapentinoids.

Ziconotide Ziconotide (SNX–111; Prialt), also called intrathecal ziconotide (ITZ) because of its administration route, is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from ''Conus magus'', a cone snail, it is the ...

, a non-gabapentinoid ω-

conotoxin A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Cono ...

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

binds to the

s and has analgesic effects 1000 times stronger than

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

. Gabapentinoids are selective for the α₂δ site, but

non-selective In biochemistry and pharmacology, a ligand is a Chemical substance, substance that forms a Complex (chemistry), complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-lig ...

when they bind to the calcium channels complex. They act on the α₂δ site to lower the release of many

and pro-

nociceptive Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...

neurochemical A neurochemical is a small organic molecule or peptide that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals. Prominent neurochemicals Neurotransmitters and neuromodulators *Glutamate is the ...

s including

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clos ...

calcitonin gene-related peptide Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produ ...

(CGRP) and more. Gabapentinoids are absorbed from the intestines mainly by the Large neutral amino acid transporter 1 (LAT1, SLC7A5) and the Excitatory amino acid transporter 3 (EAAT3). They are one of the few drugs that use these

amino acid transporter An amino acid transporter is a membrane transport protein that transports amino acids. They are mainly of the solute carrier family. Families There are several families that function in amino acid transport, some of these include: TC# 2.A.3- ...

s. Gabapentinoids are structurally similar to the Branched-chained amino acids

L-leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

, and

L-isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

, both of which also bind to the α₂δ site. Branched-chained amino acids like l-leucine, l-isoleucine, and l-valine have many functions in the central nervous system. They modify large neutral amino acid (LNAA) transport at the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

, and reduce the synthesis neurotransmitter of neurotransmitters derived from aromatic-amino acids notably

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

from

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

, and

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a subst ...

s from

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

and

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

. This may be relevant to the

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

of gabapentinoids. Gabapentin was designed by researchers at

Parke-Davis Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...

to be an analogue of the

GABA that could more easily cross the

and was first described in 1975 by Satzinger and Hartenstein. Gabapentin was first approved for

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

, mainly as an add-on treatment to partial seizures. Gabapentinoids are

GABA analogue A GABA analogue is a compound which is an analogue or derivative of the neurotransmitter gamma-Aminobutyric acid (GABA) (the IUPAC of which is 4-aminobutanoic acid). Many GABA analogues are used as drugs, especially as anticonvulsants, sedative ...

s, but they do not bind to the

GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

s, do not convert into or another

GABA receptor agonist A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three ...

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'', and do not directly modulate GABA

transport Transport (in British English), or transportation (in American English), is the intentional movement of humans, animals, and goods from one location to another. Modes of transport include air, land (rail and road), water, cable, pipeline, an ...

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

. Phenibut and

, two structurally related compounds are exceptions as they mainly act on the

GABA B receptor GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpolariz ...

. Also, gabapentin, but not pregabalin, has been found to activate K_vvoltage-gated potassium channels ( KCNQ). Despite this, gabapentinoids mimic GABA activity by inhibiting

. Gabapentinoids prevent delivery of the calcium channels to the cell membrane, and disrupt interactions of α₂δ with

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...

neurexin Neurexins (NRXN) are a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular dom ...

s, and

thrombospondin Thrombospondins (TSPs) are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins. The first member of the family, thrombospondin 1 (T ...

s. Some

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s of the dihydropyridine class used for

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

weakly block α₂δ. Gabapentinoids have

antiallodynic Allodynia is a condition in which pain is caused by a stimulus that does not normally elicit pain. For example, bad sunburn can cause temporary allodynia, and touching sunburned skin, or running cold or warm water over it, can be very painful. It i ...

, and

antinociceptive Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...

properties. Pregabalin and gabapentin are used in

, mainly partial seizures (focal). Gabapentinoids are not effective for

generalized seizures Generalized epilepsy is a form of epilepsy characterised by generalised seizures with no apparent cause. Generalized seizures, as opposed to focal seizures, are a type of seizure that impairs consciousness and distorts the electrical activity of ...

. They are also used for

postherpetic neuralgia Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (herpes zoster, also known as shingles). Typically, the nerve pain (neuralgia) is confined ...

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

associated with

diabetic neuropathy Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...

fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hyp ...

generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...

, and

restless legs syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...

. Pregabalin and gabapentin have many

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

uses including

Alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

and

opioid withdrawal Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, ...

smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often make ...

social anxiety disorder Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impaired ability to function in at least some aspects ...

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

chronic pain Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between Acute (medicine), acute and Chronic condition, chronic pain is sometimes determined by the amount of time since onset. Two commonly ...

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

es, tinnutus,

s and more. Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...

cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sensa ...

, and

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

. Phenibut is used in Russia, Ukraine, Belarus and Latvia to treat anxiety and to improve sleep, as in the treatment of insomnia. It is also used for various other indications, including the treatment of

asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

, depression,

alcoholism Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...

, alcohol withdrawal syndrome,

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on ...

stuttering Stuttering, also known as stammering, is a speech disorder in which the flow of speech is disrupted by involuntary repetitions and prolongations of sounds, syllables, words, or phrases as well as involuntary silent pauses or blocks in which the ...

tic A tic is a sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups.American Psychiatric Association (2000)DSM-IV-TR: Tourette's Disorder.''Diagnostic and Statistical Manual of Mental Disorders'', 4th ed., ...

s, vestibular disorders,

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initial ...

, for the prevention of

motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include d ...

, and for the prevention of anxiety before or after surgical procedures or painful diagnostic tests. Phenibut, like other GABA B agonists, is also sometimes used by body builders to increase

human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

Reuters Reuters ( ) is a news agency owned by Thomson Reuters Corporation. It employs around 2,500 journalists and 600 photojournalists in about 200 locations worldwide. Reuters is one of the largest news agencies in the world. The agency was estab ...

reported on 25 March 2010, that "

Pfizer Inc Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

violated a United States

racketeering Racketeering is a type of organized crime in which the perpetrators set up a coercive, fraudulent, extortionary, or otherwise illegal coordinated scheme or operation (a "racket") to repeatedly or consistently collect a profit. Originally and of ...

law by improperly promoting the epilepsy drug Neurontin (gabapentin). Under the

Racketeer Influenced and Corrupt Organizations Act The Racketeer Influenced and Corrupt Organizations (RICO) Act is a United States federal law that provides for extended criminal penalties and a civil cause of action for acts performed as part of an ongoing criminal organization. RICO was en ...

the penalty is automatically tripled, so the finding will cost Pfizer $141 million." The case stems from a claim from Kaiser Foundation Health Plan Inc. that "it was misled into believing Neurontin was effective for off-label treatment of migraines, bipolar disorder and other conditions. Pfizer argued that Kaiser physicians still recommend the drug for those uses", and that "the insurer's website also still lists Neurontin as a drug for neuropathic pain." In some cases, gabapentinoids are

d and provide similar effects to

s and gamma-hydroxybutyric acid (GHB). The

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

placed a

black box warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it ...

on Neurontin (gabapentin), and Lyrica (pregabalin), for serious

breathing problems Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing dis ...

. Mixing gabapentinoids with

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

GHB ''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...

, or any other depressant is potentially deadly. Common

side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

of gabapentinoids include

increased appetite Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...

shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...

, involuntary eye movements (

), memory issues, uncontrollable jerking motions,

auditory hallucination An auditory hallucination, or paracusia, is a form of hallucination that involves perceiving sounds without auditory stimulus. While experiencing an auditory hallucination, the affected person would hear a sound or sounds which did not come from t ...

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

, and

myoclonic seizures Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

. An

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

of gabapentinoids usually consists of severe drowsiness, severe ataxia, blurred vision,

slurred speech Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effective ...

, severe uncontrollable jerking motions, and

. Like most anticonvulsants, pregabalin and gabapentin have an increased risk of suicidal thoughts and behaviors. Gabapentinoids, like all

s are known to cause

angioedema Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ...

. Taking them with an

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

can increase the toxic effects of Gabapentinoids. They may also enhance the fluid-retaining effect of certain anti-diabetic agents (

thiazolidinedione The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used i ...

s). It is not known if they cause

gingival enlargement Gingival enlargement is an increase in the size of the gingiva (gums). It is a common feature of gingival disease. Gingival enlargement can be caused by a number of factors, including inflammatory conditions and the side effects of certain medica ...

like other

s. Gabapentinoids are excreted by the kidney mostly in their original form. Gabapentinoids can build up in the body when someone has

renal failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. This usually presents itself as

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

, and an altered mental state. It is unclear if it is safe to use Gabapentinoids during pregnancy with some studies showing potential harm.

Physical Physical may refer to: *Physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally co ...

or physiological dependence does occur during long-term use of gabapentinoids. Following abrupt or rapid discontinuation of pregabalin and gabapentin people report

withdrawal symptoms Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of wit ...

like insomnia,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

flu-like symptoms Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...

, anxiety, depression,

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychologi ...

confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

, and gastrointestinal complaints. Acute withdrawal from baclofen and phenibut may also cause auditory and visual

s, and acute

. Baclofen withdrawal can be more intense if it is administered

intrathecally Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain ...

or for long periods of time. If Baclofen or Phenibut is used for long periods of time it can resemble intense

. To minimize

Baclofen or Phenibut should be tapered down slowly. Abrupt withdrawal from Phenibut or

Baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

could be possibly be life-threatening, because of it’s mechanism of action. Abrupt withdrawal can cause rebound seizures and severe agitation. *

Gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...

(Neurontin) *

Gabapentin Enacarbil Gabapentin enacarbil (Horizant () (), Regnite (in Japan)) is an anticonvulsant and analgesic drug of the gabapentinoid class, and a prodrug to gabapentin. It was designed for increased oral bioavailability over gabapentin, and human trials show ...

(Horizant, Regnite) * Gabapentin Extended-Release (Gralise) *

Pregabalin Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety disord ...

(Lyrica) * Phenibut (Anvifen, Fenibut, Noofen) *

(Lioresal) * Mirogabalin (Tarlige) (Japan Only) Not approved: *

Imagabalin Imagabalin ( INN, USAN; PD-0332334) was an investigational drug that acted as a ligand for the α2δ subunit of the voltage-dependent calcium channel, with some selectivity for the α2δ1 subunit over α2δ2. It was under development by Pfizer ...

* Tolibut * 4-Flurophenibut * HSK16149 * Trans-4 and cis-4- 8Ffluorogabapentin (α2δ

PET Imaging Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

) * 4-Methylpregabalin *

PD-217,014 PD-217,014 is a drug developed by Pfizer and related to gabapentin, which similarly binds to the α2δ calcium channels ( 1 and 2). It was developed as a potentially more potent successor to gabapentin and pregabalin Pregabalin, sold under ...

Atagabalin Atagabalin (PD-0200,390) is a drug developed by Pfizer and related to gabapentin, which similarly binds to the α2δ calcium channels ( 1 and 2). It was under development as a treatment for insomnia, but was discontinued following unsatisfactor ...

* Arbaclofen * Saclofen

Endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

(Not

Gabapentinoids Gabapentinoids, also known as α2δ ligands, are a class of drugs that are chemical derivative, derivatives of the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) (i.e., GABA analogues) which channel blocker, block Voltage-dependent c ...

, endogenous BCAA amino acids that bind to α₂δ: *

Calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

Isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...

Leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

Valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotonat ...

Aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

Other α2δ ligands: *

Phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

* NP-118809 * Gababutin *

(Approved for pain) *

Ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

* Dextrothyroxine (

Agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of α2δ instead of inhibiting it) * Ethioninie * Suloctidil *

Terodiline Terodiline is a drug used in urology as an antispasmodic. It relaxes the smooth muscle and used to reduce bladder tone in treatment of urinary frequency and incontinence. Muscle relaxation caused by terodiline, is probably due to its anticholine ...

Bepridil Bepridil (trade name Vascor) is an diamine calcium channel blocker once used to treat angina pectoris. It is no longer sold in the United States. It is nonselective. It has been discussed as a possible option in the treatment of atrial fibrilla ...

Opioids

Contrary to popular misconception, opioids are not depressants in the classical sense. They do produce central nervous system depression, however, they also excite certain areas of the central nervous system. To remain true to the term 'depressant' – opioids cannot be classified as such. For opioid agonists and

opium Opium (or poppy tears, scientific name: ''Lachryma papaveris'') is dried latex obtained from the seed capsules of the opium poppy ''Papaver somniferum''. Approximately 12 percent of opium is made up of the analgesic alkaloid morphine, which i ...

derivatives The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics * Brzozowski derivative in the theory of formal languages * Formal derivative, an ...

, these are classified differently.

Analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

narcotic The term narcotic (, from ancient Greek ναρκῶ ''narkō'', "to make numb") originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates ...

correctly identifies these drugs. However, they do have depressant actions nonetheless. *

Morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

Heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...

Codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

Hydrocodone Hydrocodone, also known as dihydrocodeinone, is an opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe en ...

Oxycodone Oxycodone, sold under various brand names such as Roxicodone and OxyContin (which is the extended release form), is a strong, semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive and a commonly ...

Methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...

Piperidinediones

Piperidinedione Glutarimide is the organic compound with the formula (CH2)3(CO)2NH. It is a white solid. The compound forms upon dehydration of the amide of glutaric acid. Glutarimide is sometimes called 2,6-piperidinedione. It is the core of a variety of dru ...

s are a class of depressants that are not used anymore. There are Piperidinediones that are used for other purposes like

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

br>
https://books.google.ca/books?id=tsjrCAAAQBAJ&pg=PA14&redir_esc=y#v=onepage&q&f=fals

. The Piperidinedione class is very structurally similar to

s. Piperidinediones inclide Glutethimide, Methyprylon,

Pyrithyldione Pyrithyldione (Presidon, Persedon) is a psychoactive drug invented in 1949. An improved method of manufacture was patented by Roche in 1959. It was used as a hypnotic or sedative and presumed to be less toxic than barbiturates. Today, this sub ...

Glutarimide Glutarimide is the organic compound with the formula (CH2)3(CO)2NH. It is a white solid. The compound forms upon dehydration of the amide of glutaric acid. Glutarimide is sometimes called 2,6-piperidinedione. It is the core of a variety of dru ...

, and

Aminoglutethimide Aminoglutethimide (AG), sold under the brand names Elipten, Cytadren, and Orimeten among others, is a medication which has been used in the treatment of seizures, Cushing's syndrome, breast cancer, and prostate cancer, among other indications. ...

. The first 3, (Glutethimide, Methyprylon, Pyrithyldione) are central nervous depressants. The Piperidinedione depressants, specifcally Glutethimide is a positive modulator of the GABA_A

anion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

. The drug increases inhibitory GABAergic tone and causes neuro-inhibition of the cortical and

limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...

s, observed clinically as a

sedative-hypnotic A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

effec

Glutethimide is also a potent inhibitor of the CYP2D6, CYP 2D6 enzyme in the liver. This enzyme is responsible for converting many drugs from

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...

s to

s and

s. Due to its effects on the conversion of opioids, it was highly abused and mixed with opioids like codeine. Codeine needs to get

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

in the liver to have its

psychoactive A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

and

effects. Mixing codeine with the Piperidinedione Glutethimide allowed more codeine to be converted into morphine in the body; this increasing its effect. This was known as "hits", "cibas and codeine", "Dors and 4s". Glutethimide was believed to be safer than

s, but many people died from the drug. Demand was high in the United States at one point. Production of glutethimide was discontinued in the US in 1993 and in several eastern European countries, most notably Hungary, in 2006. Glutethimide

withdrawal Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * ''Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from a ban ...

is intense and resembles

barbiturate withdrawal Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as ...

. It features

s and

; typical of a depressant withdrawal. In the 1970s, there were reports of

neonatal withdrawal Neonatal withdrawal or neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome of infants after birth caused by ''in utero'' exposure to drugs of dependence, most commonly opioids. Common signs an ...

from glutethimide. Infants born to mothers addicted to glutethimide responded well initially, then had recurrence of symptoms about 5 days later, including overactivity, restlessness,

hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate upper disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by highe ...

, hypotonus, vasomotor instability, incessant crying, and general irritability. Glutethimide withdrawal featured severe agitation,

and

s which could be fatal. Overdose causes stupor or

and

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...

. * Methyprylon (Dimerin, Methyprylone, Noctan, Noludar) * Pyrithyldione (Presidon, Pyridion, Pyridione, Pyrithyldion, Pyrithyldione) * Piperidione (Ascron, Dihyprylon, Dihyprylone, Sedulon, Tusseval) (Withdrawan before approval) * Glutethimide (Doriden)

Quinazolinone

Quinazolinones are a class of depressants that are rarely used anymore. Quinazolinone have powerful sedative, hypnotic, and anxiolytic effects. Quinazolinones structures are very similar to some antibiotics. Quinazolines main mechanism of action is binding to the GABA_A receptor. It does not bind to the

, neurosteroid, or

benzodiazepine site The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor o ...

. Instead it binds on a site right betwen the GABRB2 (β2) and (α1)

GABRA1 Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the ''GABRA1'' gene. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chlor ...

proteins on the GABA_A receptor. The

etomidate Etomidate (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardiove ...

and

Anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

loreclezole may also bind to this site.

Overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

on Quinazolinone sometimes causes effects that are the opposite of Quinazolinone like sedation. Overdose consists of

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

hypertonia Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending ...

, myoclonic twitches,

, euphoria, muscular hyperactivity, agitated delirium,

, and tonic-clonic seizures. In 1982 2,764 people visited US emergency rooms from overdosing on Quinazolinones, specifically Methaqualone. Mixing Quinazolines with another depressant is possibly fatal. Death from a Quinazolinone overdose is usually caused by death through

cardiac The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

respiratory arrest Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long p ...

. Overdose resembles

/ carbamate overdose. Quinazolinones

occurs when someone has become dependent on a quinazolinone substance and stops using them. Quinazolinone withdrawal resembles

and carbamate withdrawal. It usually consists of restlessness,

and

confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

; which could cause death, EEG photoparoxysmal response, myoclonic twitches,

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

, and

irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...

. Methaqualone hydrochloride, a Quinazolinone

and

is referred to as "quaaludes" "ludes" and "disco biscuits". Methaqualone was very commonly

abused Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...

in the western world during the 1960s and 1970s. Methaqualone was mainly prescribed for

as it was thought to be safer than

s and carbamate

Methaqualone became highly abused by people and celebrities after it's introduction in 1965. Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and

Syed Husain Zaheer Syed Husain Zaheer was an Indian chemist, politician and the director general of the Council of Scientific and Industrial Research (CSIR), the largest research and development organisation in India. Prior to taking up the directorship of CSIR, H ...

, who were conducting research on finding new

antimalarial medication Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...

s. The drug name "Quaalude" (Methaqualone) is a

portmanteau A portmanteau word, or portmanteau (, ) is a blend of wordspsychological addictiveness, widespread

, and illegal recreational use. Non-benzodiazepines, and

s are now uses to treat

instead. Methaqualone is now a schedule I substance. Some quinazolinone analogues are still sold online. They come with risks of

s. Large doses of Methaqualone cause euphoria,

, increased sexuality,

sociability Social behavior is behavior among two or more organisms within the same species, and encompasses any behavior in which one member affects the other. This is due to an interaction among those members. Social behavior can be seen as similar to an ...

, and sedation. Today Methaqualone is widely abused in

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring countri ...

. Many celebrities have used Quinazolinone; specifically Methaqualone. Bill Cosby admitted to casual sex involving recreational use of

Methaqualone Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude ( ) and Sopor among others, which contained 300 mg of methaqualone, and sold as a combination drug under the brand name Mandrax, which contained 250 mg met ...

(Quaaludes). 18 year old actor Anissa Jones died at 18 from an overdose of

cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...

, PCP,

, and the barbiturate

Seconal Secobarbital (as the sodium salt, originally marketed by Eli Lilly and Company for the treatment of insomnia, and subsequently by other companies as described below, under the brand name Seconal) is a short-acting barbiturate derivative drug that ...

Billy Murcia Billy Murcia (October 9, 1951 – November 6, 1972) was the original drummer for the New York Dolls.Jacobson, Mark"The Icon: Doll Face" ''New York (magazine)'', September 23, 2002. Accessed May 28, 2009. "Then came the sad pictures: Johnny and ...

a drummer for the rock band

New York Dolls New York Dolls were an American rock band formed in New York City in 1971. Along with the Velvet Underground and the Stooges, they were one of the first bands of the early punk rock scenes. Although the band never achieved much commercial succe ...

died at 21 when he drowned in a bathtub while overdosing on

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...

and Methaqualone.

Cloroqualone Cloroqualone is a quinazolinone-class GABAergic and is an analogue of methaqualone developed in the 1980s and marketed mainly in France and some other European countries. It has sedative and antitussive properties resulting from its agonist act ...

was a Quinazolinone that binded to the GABA_A and

sigma-1 receptor The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gene. ...

. It had useful cough suppressant effects and weaker sedative effects than Methaqualone. But it was withdrawan due to its potential for abuse and overdose.

Diproqualone Diproqualone is a quinazolinone class GABAergic and is an analogue of methaqualone developed in the late 1950s by a team at Nogentaise de Produits Chimique. It was marketed primarily in France and some other European countries. It has sedative ...

is a Quinazolinone that is still used today. Diproqualone has

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

and

properties, resulting from its agonist activity at the β subtype of the GABA_a receptor, antagonist activity at all

histamine receptor The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand. There are four known histamine receptors: * H1 receptor * H2 receptor * H3 receptor * H4 receptor Comparison There ...

s, inhibition of the

cyclooxygenase-1 Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the ''PTGS1'' gene. In humans it is one of two cyclooxygenases. ...

enzyme, and possibly its agonist activity at both the

and

sigma-2 receptor The sigma-2 receptor (σ2R) is a sigma receptor subtype that has attracted attention due to its involvement in diseases such as cancer and neurological diseases. It is currently under investigation for its potential diagnostic and therapeutic use ...

. Diproqualone is used primarily for the treatment of inflammatory pain associated with

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

and

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

, and more rarely for treating

and

neuralgia Neuralgia (Greek ''neuron'', "nerve" + ''algos'', "pain") is pain in the distribution of one or more nerves, as in intercostal neuralgia, trigeminal neuralgia, and glossopharyngeal neuralgia. Classification Under the general heading of neuralg ...

. Diproqualone is the only analogue of

that is still in widespread clinical use, due to its useful

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...

and

effects in addition to the

and

actions common to other drugs of this class. There are still some concerns about the potential of diproqualone for

and

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

, and so it is not sold as a pure drug but only as the camphosulfonate salt in combination mixtures with other medicines such as

ethenzamide Ethenzamide (2-ethoxybenzamide) is a common analgesic and anti-inflammatory drug that is used for the relief of fever, headaches, and other minor aches and pains. It is also an ingredient in numerous cold medications and many prescription analge ...

Etaqualone Etaqualone (Aolan, Athinazone, Ethinazone) is a quinazolinone-class GABAergic and is an analogue of methaqualone that was developed in the 1960s and marketed mainly in France and some other European countries. It has sedative, hypnotic, muscle ...

is a

quinazolinone Quinazolinone is a heterocyclic chemical compound, a quinazoline with a carbonyl group in the C4N2 ring. Two isomers are possible: 2-quinazolinone and 4-quinazolinone, with the 4-isomer being the more common. These compounds are of interest in me ...

-class depressant. It has

and

central nervous system depressant A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the l ...

properties. It was highly abused, and had high risk for overdose. Users would snort or smoke the free base Etaqualone hydrochloride salt.

Methylmethaqualone Methylmethaqualone (MMQ) is a quinazolinone and an analogue of methaqualone that has similar sedative and hypnotic properties to its parent compound (resulting from its agonist activity at the β subtype of the GABAA receptor), and is much mor ...

is an analogue of Methaqualone with similar

and

effects. Methylmethaqualone differs from methaqualone by 4-methylation on the phenyl ring. It produces

convulsions A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

at only slightly above the effective sedative dose. It would appear that this compound was sold on the black market in Germany as a

designer drug A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Des ...

analogue of methaqualone.

Nitromethaqualone Nitromethaqualone is an analogue of methaqualone Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude ( ) and Sopor among others, which contained 300 mg of methaqualone, and sold as a combination drug under th ...

is a quinazolinone depressant with 10x more powerful

and

effects than Methaqualone. Quinazolinone's: * Alfoqualone (Arofuto) *

(Aolan, Athinazone, Ethinazone) *

Mebroqualone Mebroqualone (MBQ) is a quinazolinone-class GABAergic and is an analogue of mecloqualone that has similar sedative and hypnotic properties to its parent compound, resulting from its agonist activity at the β subtype of the GABAa receptor. It w ...

(MBQ) *

Mecloqualone Mecloqualone (Nubarene, Casfen) is a Quinazolinone-class GABAergic and is an analogue of methaqualone that was first made in 1960 and marketed mainly in France and some other European countries. It has sedative, hypnotic, and anxiolytic proper ...

(Nubarene, Casfen) *

(Quaalude, Sopor, Mandrax) *

SL-164 SL-164, also known as dicloqualone or DCQ is an analogue of methaqualone Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude ( ) and Sopor among others, which contained 300 mg of methaqualone, and sold as a ...

(Dicloqualone, DCQ)

Miscellaneous

Alpha Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whic ...

and

s (

carvedilol Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is gen ...

propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...

atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...

, etc.) *

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

s (

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...

, hyoscyamine, scopolamine, etc.) *

s (

topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...

lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut synd ...

, etc.) *

Antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

s (

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into a vein ...

doxylamine Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. In combination with pyridoxine ( vitamin B6), it is also used to treat morning sickness in pre ...

promethazine Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...

, etc.) *

Antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...

s (

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar dis ...

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

, etc.) *

Hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

s (

zolpidem Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behaviora ...

zopiclone Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat insomnia, difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone inc ...

chloral hydrate Chloral hydrate is a geminal diol with the formula . It is a colorless solid. It has limited use as a sedative and hypnotic pharmaceutical drug. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichl ...

eszopiclone Eszopiclone, sold under the brand-name Lunesta among others such as Night Calm in Egypt, is a medication used in the treatment of insomnia. Evidence supports slight to moderate benefit up to six months. It is taken orally. Common side effects i ...

, etc.) *

Muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeu ...

s (baclofen, phenibut, carisoprodol,

cyclobenzaprine Cyclobenzaprine (sold under the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...

, etc.) *

Sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but t ...

s (

gamma-hydroxybutyrate ''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...

, etc.)

Methods of intake

Combining multiple depressants can be very dangerous because the central nervous system's depressive properties have been proposed to increase exponentially instead of linearly. This characteristic makes depressants a common choice for deliberate overdoses in the case of

suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and s ...

. The use of alcohol or benzodiazepines along with the usual dose of heroin is often the cause of overdose deaths in opiate addicts.

References

External links

Painfully Obvious – A Community Resource

Fact sheets and Harm Reduction Strategies About Depressants and Other Recreational Drugs

U.S. Department of Human and Health Services: Drug Categories for Substances of Abuse

*

National Institute on Drug Abuse The National Institute on Drug Abuse (NIDA) is a United States federal government research institute whose mission is to "advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual a ...

:
NIDA for Teens: Prescription Depressant Medications
. {{Recreational drug use Psychoactive drugs Drugs acting on the nervous system Health effects of alcohol