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 receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that signal chloride and diminish further action potentials. 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 too produce sedative effects. Furthermore, they lead to changes in gene transcription.
GABAA receptor
Agonists
- Barbiturates (in high doses)
- Bamaluzole
- GABA
- Gabamide
- GABOB
- Gaboxadol
- Ibotenic acid
- Isoguvacine
- Isonipecotic acid
- Muscimol
- Phenibut
- Picamilon
- Progabide
- Propofol
- Quisqualamine
- SL 75102
- Thiomuscimol
PAMs
- Alcohols (e.g., ethanol, isopropanol)
- Avermectins (e.g., ivermectin)
- Barbiturates (e.g., phenobarbital)
- Benzodiazepines (e.g., diazepam, alprazolam)
- Bromides (e.g., potassium bromide)
- Carbamates (e.g., meprobamate, carisoprodol)
- Chloralose
- Chlormezanone
- Clomethiazole
- Dihydroergolines (e.g., ergoloid (dihydroergotoxine))
- Etazepine
- Etifoxine
- Imidazoles (e.g., etomidate)
- Kavalactones (found in kava)
- Loreclezole
- Neuroactive steroids (e.g., allopregnanolone, ganaxolone)
- Nonbenzodiazepines (e.g., zaleplon, zolpidem, zopiclone, eszopiclone)
- Petrichloral
- Phenols (e.g., propofol)
- Piperidinediones (e.g., glutethimide, methyprylon)
- Propanidid
- Pyrazolopyridines (e.g., etazolate)
- Quinazolinones (e.g., methaqualone)
- Skullcap constituents
- Stiripentol
- Sulfonylalkanes (e.g., sulfonmethane, tetronal, trional)
- Valerian constituents (e.g., valeric acid, valerenic acid)
- Volatiles/gases (e.g., chloral hydrate, chloroform, diethyl ether, sevoflurane)
GABAB receptor
Agonists
- 1,4-Butanediol
- Baclofen
- GABA
- Gabamide
- GABOB
- gamma-Butyrolactone (GBL)
- gamma-Hydroxybutyric acid (GHB)
- gamma-Hydroxyvaleric acid (GHV)
- gamma-Valerolactone (GVL)
- Lesogaberan
- Phenibut
- Picamilon
- Progabide
- SL-75102
- Tolgabide
GABAA-ρ receptor
Agonists
PAMs
- Neuroactive steroids (e.g., allopregnanolone, THDOC, alphaxolone)
Indirect GABA Agonists
Discussion
Many commonly used sedative and anxiolytic drugs that affect the GABA receptor complex aren't agonists. These drugs are known as positive allosteric modulators, and while they do bind to the GABA receptors, they 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.
Most general anaesthetics are PAMs of GABA-A receptor. Positive allosteric modulators work by increasing the frequency with which the chlorine 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.
Alcohol is an indirect GABA agonist. GABA is the major inhibitory neurotransmitter 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.
References
External links
- GABA agonists at the US National Library of Medicine Medical Subject Headings (MeSH)
- MeSH list of agents 82018755