Pemoline, sold under the brand name Cylert among others, is a

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 ...

medication which has been used in the treatment of

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-inappr ...

(ADHD) and

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...

. It has been discontinued in most countries to due to rare but serious problems with liver toxicity. The medication was taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

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 pemoline include

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 ...

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...

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 ...

, and

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 ...

s. Rarely, the medication can cause serious

liver damage Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...

, and this can result in liver transplantation or death. Pemoline is a psychostimulant and acts as a selective

dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopa ...

and

releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the synapse, release of a monoamine neurotransmitter from the synapse, presynaptic neuron into the synapse, leading to an increase in the extracellular conc ...

. Hence, it functions as an indirect

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 ...

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

s. Pemoline has little effect on

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

and hence has minimal or no

cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

sympathomimetic Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...

effects, in contrast to many other stimulants. Pemoline was synthesized in 1913 but was not discovered to be a stimulant until the 1930s and was not used in the treatment of ADHD until 1975. It was withdrawn due to liver toxicity in many countries between 1997 and 2005, including the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

. However, it remains available in

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

for the treatment of narcolepsy at lower doses than used for ADHD. Pemoline is a schedule IV

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...

in the United States due to its relation to other stimulants and a

potential for misuse Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

. It seems to have less misuse potential than other stimulants.

Medical uses

Pemoline has been used in the treatment of

ADHD 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-inapp ...

and

. It has also been used in the treatment of

excessive daytime sleepiness Excessive daytime sleepiness (EDS) is characterized by persistent sleepiness and often a general lack of energy, even during the day after apparently adequate or even prolonged nighttime sleep. EDS can be considered as a broad condition encompass ...

. The medication was typically used at doses of 18.75 to 112.5mg once per day in the treatment of ADHD, with the effective dose for most people being in the range of 56.25 to 75mg. The

onset of action Onset of action is the duration of time it takes for a drug's effects to come to prominence upon administration. With oral administration, it typically ranges anywhere from 20 minutes to over an hour, depending on the drug in question. Other meth ...

of pemoline is gradual and therapeutic benefits may not occur until the third or fourth weeks of use. This may be due to a cautious low initial starting dose of 37.5mg and gradual titration in dose upwards over several weeks.

Available forms

Pemoline was available in the form of 18.75, 37.5, and 75mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

immediate-release Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a spe ...

tablets (Cylert) as well as 37.5mg oral immediate-release

chewable tablet A tablet (also known as a pill) is a pharmaceutical oral dosage form (''oral solid dosage'', or OSD) or solid unit dosage form. Tablets may be defined as the solid unit dosage form of medicament or medicaments with suitable excipients. It compri ...

s. It was provided mainly in the form of the free base but also as the

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...

Side effects

s of pemoline include

, and

s. It has minimal

side effects. Pemoline is described as a lower-efficacy/milder stimulant than classical stimulants like

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

s and

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...

and is said to have fewer side effects than them.

Liver toxicity

Rarely, pemoline is implicated in causing

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

. Because of this, the FDA recommended that regular liver tests be performed in those treated with it. Since being introduced, it has been linked with at least 21 cases of liver failure, of which 13 resulted in liver replacement or death. Approximately 1–2% of patients taking the drug show elevated levels of liver

transaminase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α- keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid ...

enzymes, a marker for liver toxicity, though serious cases are rare. Over 200,000 children with ADHD were prescribed pemoline in the United States and Canada alone during the approximate 25 years that it was available, plus a smaller number of adults prescribed it for other indications (and not including prescriptions in the rest of the world). As such, the number of liver failure cases was statistically not that large. However the reactions proved idiosyncratic and unpredictable, with patients sometimes taking the drug with no issue for months or even years, before suddenly developing severe liver toxicity. There was no clear exposure–toxicity relationship, and no characteristic liver

pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...

findings. Some patients showed as little as one week between first appearance of

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

and complete liver failure, and some of the patients that developed liver failure had not showed elevated liver transaminase levels when tested previously. On the other hand, there are no cases of liver failure associated with pemoline in Japan, although it is used at lower doses and is only prescribed for the niche indication of narcolepsy in this country.

Overdose

Overdose of pemoline may present with

choreoathetosis Choreoathetosis is the occurrence of involuntary movements in a combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing). It is caused by many different diseases and agents. It is a symptom of several diseases ...

symptoms.

Interactions

Other stimulants and

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...

s are

contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

with pemoline.

Pharmacology

Pharmacodynamics

The

pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...

of pemoline are poorly understood and its precise

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

hasn't been definitively determined. However, pemoline has similar activity and effects to those of other psychostimulants, and in animals the medication appears to act as a

and

. By increasing dopamine levels in the brain, it functions as an indirect

s. In contrast to most other stimulants, pemoline appears to produce no significant

central Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known as ...

peripheral A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...

noradrenergic Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

effects. As a result, it has minimal or no

effects. Pemoline is described as a selective dopamine reuptake inhibitor that only weakly stimulates dopamine release. While drugs like

dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...

and

are classified as schedule II and have considerable misuse potential, pemoline is listed as schedule IV (non-narcotic). In studies conducted on primates, pemoline fails to demonstrate a potential for self-administration. It is thought to have little potential for abuse and dependence. Nonetheless, misuse may theoretically occur owing to its similarity to other psychostimulants.

Pharmacokinetics

Studies of the

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

of pemoline in humans are very limited. The time to peak levels of pemoline is 2 to 4hours. Peak levels have been reported to be in the range of 2 to 4.5μg/mL. Steady-state levels of pemoline are reached in 2 to 3days. Pemoline is variously reported to have no significant

plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse t ...

or to have 50% plasma protein binding. Pemoline is

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 The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

. Its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s include pemoline conjugate, pemoline dione, mandelic acid, and unidentified polar metabolites. Pemoline is

excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

mainly by the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s with around 50% excreted in unchanged form and only minor amounts present as metabolites. The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of pemoline is 7 to 12hours. The half-life is 7hours in children but may increase to 11 to 12hours with age. The relatively long half-life of pemoline allows for once-daily administration. No differences in the pharmacokinetics of pemoline were found with conventional tablets, chewable tablets swallowed, or chewable tablets chewed.

Chemistry

Pemoline is a member of the 4-

oxazolidinone 2-Oxazolidone is a heterocyclic organic compound containing both nitrogen and oxygen in a 5-membered ring. Oxazolidinones Evans auxiliaries Oxazolidinones are a class of compounds containing 2-oxazolidone in the structure. In chemistry, they are ...

class and is structurally related to other members of the class including

aminorex Aminorex (Menocil, Apiquel, aminoxaphen, aminoxafen, McN-742) is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension. In the U.S., it is an illegal Schedule I drug, mea ...

4-methylaminorex 4-Methylaminorex (4-MAR, 4-MAX) is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a s ...

clominorex Clominorex is a centrally acting sympathomimetic which is related to other drugs such as aminorex and pemoline. It was developed as an appetite suppressant by McNeil Laboratories in the 1950s. See also * 4-Methylaminorex * Aminorex * Cyclazodone ...

cyclazodone Cyclazodone is a centrally acting stimulant drug developed by American Cyanamid Company in the 1960s. The drug is related to other drugs such as pemoline and thozalinone. It displayed a favorable therapeutic index and margin of safety in compari ...

fenozolone Fenozolone (Ordinator) was developed by Laboratoires Dausse in the 1960s and is a psychostimulant related to pemoline. See also * 4-Methylaminorex * Aminorex * Clominorex * Cyclazodone * Fluminorex * Pemoline * Thozalinone Thozalinone ( US ...

fluminorex Fluminorex is a centrally acting sympathomimetic which is related to other drugs such as aminorex and pemoline. It was developed as an appetite suppressant by McNeil Laboratories in the 1950s.US Patent 3278382 - 2-amino-5-aryloxazoline compositio ...

, and

thozalinone Thozalinone (USAN) (brand name Stimsen; former developmental code name CL-39808) is a psychostimulant that has been used as an antidepressant in Europe. It has also been trialed as an anorectic. Thozalinone is described as a " dopaminergic sti ...

. The salts of pemoline in use are pemoline magnesium (free base conversion ratio .751), pemoline iron (.578), pemoline copper (.644), pemoline nickel (.578), pemoline rubidium, pemoline calcium, pemoline chromium, and chelates of the above which are identical in weight to the salt mentioned. Pemoline free base and pemoline cobalt, strontium, silver, barium, lithium, sodium, potassium, zinc, manganese, and caesium are research chemicals which can be produced in situ for experiments.DEA office of Diversion Control site: Federal Register publications of CSA schedules, 2014 Q1CRC Handbook of Chemistry & Physics Others such as lanthanide pemoline salts such as pemoline cerium can be prepared; pemoline beryllium would presumably be toxic.

Synthesis

Pemoline is synthesized by the condensation of racemic ethyl mandelate with

guanidine Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...

History

Pemoline was first synthesized in 1913Chemische Berichte, 1913, vol.46, p. 2083 but its activity was not discovered until the 1930s.Acta Academiae Aboensis, Series B: Mathematica et Physica, 1939, vol. 11, #14 p. 3,7 Pemoline was approved for the treatment of ADHD in the United States in 1975. Cases of serious liver toxicity and associated death related to pemoline in children and adolescents were reported to the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

's MedWatch between 1977 to 1996. Serious liver toxicity with pemoline was first described in the medical literature in 1984 and 1989

letters to the editor A letter to the editor (LTE) is a letter sent to a publication about an issue of concern to the reader. Usually, such letters are intended for publication. In many publications, letters to the editor may be sent either through conventional mai ...

. Clinicians were little-aware of liver toxicity with pemoline until the 1990s. Warnings for liver toxicity for pemoline were added to the

(FDA) label for the medication in December 1996 and 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 ...

was added in June 1999 along with requirements for written consent and frequent monitoring of

liver enzyme Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin tim ...

s. These warnings followed a 1995 publication on liver toxicity with pemoline. However, findings suggested that clinicians poorly followed the FDA's directives on use of pemoline. In any case, sales of pemoline in the United States increased until 1997 and declined between 1996 and 1999. Pemoline was withdrawn due to liver toxicity in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...

in September 1997, in

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

in September 1999, and in the United States in 2005. Abbott Laboratories voluntarily withdraw pemoline from the United States market in May 2005 and the FDA withdrew approval of generic pemoline in November 2005. Pemoline remains available in Japan for treatment of narcolepsy as of 2017.

Society and culture

Names

''Pemoline'' is the generic name of the drug and its , , and . Pemoline was formerly marketed under the brand names Cylert, Betanamin, Ceractiv, Hyperilex, Kethamed, Ronyl, Stimul, Tamilan, Tradon, Tropocer, and Volital.

Availability

Pemoline has been marketed in the

, the

Belgium Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...

Luxembourg Luxembourg ( ; lb, Lëtzebuerg ; french: link=no, Luxembourg; german: link=no, Luxemburg), officially the Grand Duchy of Luxembourg, ; french: link=no, Grand-Duché de Luxembourg ; german: link=no, Großherzogtum Luxemburg is a small lan ...

Spain , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = ''Plus ultra'' (Latin)(English: "Further Beyond") , national_anthem = (English: "Royal March") , i ...

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...

Switzerland ). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...

, and

Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, th ...

. It remains available in

for the treatment of narcolepsy as of 2017. However, the medication is said to be rarely used in Japan as narcolepsy is a niche indication and as clinicians are wary of the liver toxicity that it has been associated with.

Legal status

Under the

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as #Amphetamine-type stimulants, amphetamine-type stimulants, barbiturates, benzodiazepines, and Psychedelic drug, psychede ...

, it is a schedule IV

.Annual Estimates Of Requirements Of Narcotic Drugs, Manufacture Of Synthetic Drugs, Opium Production And Cultivation Of The
Pemoline is Schedule IV Non-Narcotic (Stimulant) controlled substance with a DEA ACSCN of 1530 and is not subject to annual manufacturing quotas.

Research

Fatigue

Pemoline has been studied in and reported to be effective in the treatment of

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

due to

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 ...

and

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

-related disease.

References

{{Monoamine releasing agents AbbVie brands Aminorexes Hepatotoxins Norepinephrine-dopamine releasing agents Oxazolidinones Stimulants Substances discovered in the 1910s Withdrawn drugs