Gamma-Aminobuttersäure - gamma-aminobutyric acid

A GABA receptor agonist is a drug that is an

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 ...

for one or more of 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, producing typically

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 ...

effects, and may also cause other effects such as

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 ...

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 ...

, 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 ...

effects. There are three receptors of the ''gamma''-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that are permeable to chloride ions which reduces neuronal excitability. The GABA-β receptor belongs to the class of G-Protein coupled receptors that inhibit adenylyl cyclase, therefore leading to decreased cyclic adenosine monophosphate (cAMP). GABA-α and GABA-ρ receptors produce sedative and hypnotic effects and have anti-convulsion properties. GABA-β receptors also produce sedative effects. Furthermore, they lead to changes in gene transcription.

Types

Many commonly used

and

drugs that affect the GABA receptor complex are not agonists. These drugs act instead as

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

s (PAMs) and while they do bind to the GABA receptors, they bind to an allosteric site on the receptor and cannot induce a response from the neuron without an actual agonist being present. Drugs that fall into this class exert their pharmacodynamic action by increasing the effects that an agonist has when potentiation is achieved. General anaesthetics act primarily as PAMs of GABA-A receptor. Positive allosteric modulators work by increasing the frequency with which the chloride channel opens when an agonist binds to its own site on the GABA receptor. The resulting increase in the concentration of Cl− ions in the postsynaptic neuron immediately hyperpolarizes this neuron, making it less excitable and thus inhibiting the possibility of an

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

. However, some general anaesthetics like propofol and high doses of barbiturates may not only be positive allosteric modulators of GABA-A receptors but also direct agonists of these receptors.

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 ...

is an indirect GABA agonist. GABA is the major inhibitory

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 ...

in the brain, and GABA-like drugs are used to suppress spasms. Alcohol is believed to mimic GABA's effect in the brain, binding to GABA receptors and inhibiting neuronal signaling.

GABA_A

GABA_A receptor ligands include:

Agonists

Abecarnil Abecarnil (ZK-112,119) is an anxiolytic drug from the β-Carboline family. It is one of a relatively recently developed class of medicines known as the nonbenzodiazepines, which have similar effects to the older benzodiazepine group, but with qui ...

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 (in high doses) *

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 ...

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 ...

* Bamaluzole * Fengabine * GABA * Gabamide *

GABOB γ-Amino-β-hydroxybutyric acid (GABOB), also known as β-hydroxy-γ-aminobutyric acid (β-hydroxy-GABA), and sold under the brand name Gamibetal among others, is an anticonvulsant which is used for the treatment of epilepsy in Europe, Japan, and ...

Gaboxadol Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), is a conformationally constrained derivative of the alkaloid muscimol that was first synthesized in 1977 by the Danish chemist Povl Krogsgaard-Larsen. In the early 19 ...

Ibotenic acid Ibotenic acid or (''S'')-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a chemical compound and psychoactive drug which occurs naturally in ''Amanita muscaria'' and related species of mushrooms typically found i ...

Isoguvacine Isoguvacine is a GABAA receptor agonist used in scientific research. See also * Gaboxadol * Muscimol Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of '' Amanita muscaria'' and related specie ...

* Isonipecotic acid *

Muscimol Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of '' Amanita muscaria'' and related species of mushroom. Muscimol is a potent and selective orthosteric agonist for the GABAA receptors and displa ...

* Phenibut * Picamilon *

Progabide Progabide (INN; trade name Gabrene, Sanofi-Aventis) is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist of the GABAA, GABAB, and GABAA-ρ re ...

Propofol Propofol, marketed as Diprivan, among other names, is a short-acting medication that results in a decreased level of consciousness and a lack of memory for events. Its uses include the starting and maintenance of general anesthesia, sedation f ...

Quisqualamine Quisqualamine is the α-decarboxylated analogue of quisqualic acid, as well as a relative of the neurotransmitters glutamate and γ-aminobutyric acid (GABA). α-Decarboxylation of excitatory amino acids can produce derivatives with inhibitory ...

* SL 75102 * Thiomuscimol *

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 ...

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 ...

PAMs

s (e.g.,

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 ...

isopropanol Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group (chemical formula ) it is the simple ...

) *

Avermectin The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring c ...

s (e.g.,

ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, today it is used to treat inf ...

) *

s (e.g.,

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 ...

) *

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, ...

s (e.g.,

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 ...

alprazolam 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 u ...

) *

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 (e.g.,

potassium bromide Potassium bromide ( K Br) is a salt, widely used as an anticonvulsant and a sedative in the late 19th and early 20th centuries, with over-the-counter use extending to 1975 in the US. Its action is due to the bromide ion (sodium bromide is equall ...

) *

Carbamate In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally o ...

s (e.g.,

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 ...

carisoprodol Carisoprodol, sold under the brand name Soma among others, is a medication used for musculoskeletal pain. Use is only approved for up to three weeks. Effects generally begin within half an hour and last for up to six hours. It is taken orally. ...

) *

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 ...

chloralose Chloralose (also known as α-chloralose) is an avicide, and a rodenticide used to kill mice in temperatures below 15 °C. It is also widely used in neuroscience and veterinary medicine as an anesthetic and sedative. Either alone or in combin ...

, petrichloral, and other 2,2,2-trichloroethanol

prodrugs A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

Chlormezanone Chlormezanone (marketed under the brandname Trancopal or Fenaprim) is a drug used as an anxiolytic and a muscle relaxant. Its use was discontinued in many countries from 1996 on, due to rare but serious cases of toxic epidermal necrolysis To ...

Clomethiazole Clomethiazole (also called chlormethiazole or Heminevrin) is a sedative and hypnotic originally developed by Hoffmann-La Roche in the 1930s. The drug is used in treating and preventing symptoms of acute alcohol withdrawal. It is structurally r ...

* Dihydroergolines (e.g., ergoloid (dihydroergotoxine)) * Etazepine * Etifoxine * 2-Substituted

phenols In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl groups (— O H) bonded directly to an aromatic hydrocarbon group. The simplest is phenol, . Phenolic compounds are c ...

(e.g.,

thymol Thymol (also known as 2-isopropyl-5-methylphenol, IPMP), , is a natural monoterpenoid phenol derivative of ''p''-Cymene, isomeric with carvacrol, found in oil of thyme, and extracted from ''Thymus vulgaris'' (common thyme), ajwain, and vario ...

eugenol Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, basil ...

) *

Imidazole Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...

s (e.g.,

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 ...

) *

Kavalactone Kavalactones are a class of lactone compounds found in kava roots and Alpinia zerumbet (Shell ginger). Kavalactones are under research for potential to have various psychotropic effects, including anxiolytic and sedative/ hypnotic activities. En ...

s (found in

kava Kava or kava kava (''Piper methysticum'': Latin 'pepper' and Latinized Greek 'intoxicating') is a crop of the Pacific Islands. The name ''kava'' is from Tongan and Marquesan, meaning 'bitter'; other names for kava include ''ʻawa'' (Hawaiʻi), ...

) * Loreclezole *

Neuroactive steroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was coin ...

s (e.g.,

allopregnanolone Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum d ...

ganaxolone Ganaxolone, sold under the brand name Ztalmy, is a medication used to treat seizures in people with cyclin-dependent kinase-like 5 deficiency disorder, cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD). Ganaxolone was approved ...

) *

Nonbenzodiazepine Nonbenzodiazepines (), sometimes referred to colloquially as Z-drugs (as many of their names begin with the letter "z"), are a class of psychoactive drugs that are very benzodiazepine-like in nature. They are used in the treatment of sleep proble ...

s (e.g.,

zaleplon Zaleplon, sold under the brand names Sonata among others, is a sedative-hypnotic, used to treat insomnia. It is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. It is manufactured by King Pharmaceuticals and Gedeon Richter Plc. ...

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 ...

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 ...

) *

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 (e.g.,

glutethimide Glutethimide is a hypnotic sedative that was introduced by Ciba in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused simila ...

methyprylon Methyprylon, or Noludar, is a sedative of the piperidinedione derivative family first developed by Hoffmann-La Roche. This medicine was used for treating insomnia, but is now rarely used as it has been replaced by newer drugs with fewer side eff ...

) *

Propanidid Propanidid is an ultra short-acting phenylacetate general anesthetic. It was originally introduced by Bayer in 1963 but anaphylactic reaction Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid ...

* Pyrazolopyridines (e.g., etazolate) *

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 med ...

s (e.g.,

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 ...

) *

Skullcap Skullcap or skull cap usually refers to various types of headgear. Specifically it may refer to: Headwear * Beanie (seamed cap) * Biretta, forming part of some clerical, academic or legal dress * Calotte (Belgium), a skullcap worn by students at ...

constituents (e.g.,

Baicalein Baicalein (5,6,7-trihydroxyflavone) is a flavone, a type of flavonoid, originally isolated from the roots of ''Scutellaria baicalensis'' and '' Scutellaria lateriflora''. It is also reported in '' Oroxylum indicum'' (Indian trumpetflower) and ' ...

) *

Stiripentol Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder. The most common side effects include loss of appetite, weight loss, insomnia (difficu ...

* Disulfonylalkanes (e.g.,

sulfonmethane Sulfonmethane (Sulfonomethane, Sulfonal, Acetone diethyl sulfone) is a chemical compound first synthesized by Eugen Baumann in 1888 and introduced as a hypnotic drug by Alfred Kast later on, but now superseded by newer and safer sedatives. Its ap ...

tetronal Tetronal is a sedative-hypnotic and anesthetic drug with GABAergic action Action may refer to: * Action (narrative), a literary mode * Action fiction, a type of genre fiction * Action game, a genre of video game Film * Action film, a genre ...

trional Trional (Methylsulfonal) is a sedative-hypnotic and anesthetic drug with GABAergic actions. It has similar effects to sulfonal, except it is faster acting. History Trional was prepared and introduced by Eugen Baumann and Alfred Kast in 1888. ...

) * Valerian constituents (e.g.,

valeric acid Valeric acid or pentanoic acid is a straight-chain alkyl carboxylic acid with the chemical formula . Like other low-molecular-weight carboxylic acids, it has an unpleasant odor. It is found in the perennial flowering plant ''Valeriana officina ...

valerenic acid Valerenic acid is a sesquiterpenoid constituent of the essential oil of the valerian plant. Valerian is used as a herbal sedative which may be helpful in the treatment of insomnia. Valerenic acid may be at least partly responsible for valeri ...

) *

Volatile organic compounds Volatile organic compounds (VOCs) are organic compounds that have a high vapour pressure at room temperature Colloquially, "room temperature" is a range of air temperatures that most people prefer for indoor settings. It feels comfortable to a ...

(e.g.,

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

diethyl ether Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...

sevoflurane Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflura ...

)

GABA_B

GABA_B receptor ligands include:

Agonists

1,4-Butanediol 1,4-Butanediol, colloquially known as BD or BDO, is a primary alcohol, and an organic compound, with the formula HOCH2CH2CH2CH2OH. It is a colorless viscous liquid. It is one of four stable isomers of butanediol. Synthesis In industrial sy ...

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 ...

* GABA * Gabamide *

* gamma-Butyrolactone (GBL) *

gamma-Hydroxybutyric acid ''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. ...

(GHB) * gamma-Hydroxyvaleric acid (GHV) *

gamma-Valerolactone γ-Valerolactone (GVL) is an organic compound with the formula C5H8O2. This colourless liquid is one of the more common lactones. GVL is chiral but is usually used as the racemate. It is readily obtained from cellulosic biomass and is a potenti ...

(GVL) * Lesogaberan * Phenibut * 4-Fluorophenibut * Picamilon *

* SL-75102 *

Tolgabide Tolgabide (INN; development code SL-81.0142) is a drug which was patented by Synthélabo as an anticonvulsant but was never marketed. It is an analogue of progabide and acts similarly to it as a prodrug of GABA, and therefore as an indirect ...

PAMs

* ADX-71441

GABA_A-ρ

GABA_A-ρ receptor ligands include:

Agonists

* CACA *

CAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

* GABA *

* N⁴-Chloroacetylcytosine arabinoside * Picamilon *

PAMs

s (e.g.,

THDOC Tetrahydrodeoxycorticosterone (abbreviated as THDOC; 3α,21-dihydroxy-5α-pregnan-20-one), also referred to as ''allotetrahydrocorticosterone'', is an endogenous neurosteroid. It is synthesized from the adrenal hormone deoxycorticosterone by t ...

alphaxolone Alfaxalone, also known as alphaxalone or alphaxolone and sold under the brand name Alfaxan, is a neuroactive steroid and general anaesthetic, general anesthetic which is used currently in veterinary practice as an General anaesthesia#Induction, i ...

)

References

External links

* * {{Neuromodulation Drugs acting on the nervous system