GABA receptor agonist
AGABA receptor agonistis a drug that is anagonistfor one or more of theGABA receptors,producing typicallysedativeeffects, and may also cause other effects such asanxiolytic,anticonvulsant,andmuscle relaxanteffects.[1]There are three receptors of thegamma-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[edit]
Many commonly usedsedativeandanxiolyticdrugs that affect the GABA receptor complex are not agonists. These drugs act instead aspositive allosteric modulators(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 whenpotentiationis 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 anaction potential.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.
Alcoholis an indirectGABAagonist. GABA is the major inhibitoryneurotransmitterin 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.
GABAA[edit]
GABAAreceptorligands include:
Agonists[edit]
- Abecarnil[2]
- Barbiturates(in high doses)[3]
- Etomidate[4]
- Eszopiclone
- Bamaluzole[2]
- Fengabine[2]
- GABA
- Gabamide
- GABOB
- Gaboxadol[2]
- Ibotenic acid
- Isoguvacine
- Isonipecotic acid
- Muscimol[2]
- Phenibut
- Picamilon
- Progabide
- Propofol[4][5]
- Quisqualamine
- SL 75102
- Thiomuscimol
- Topiramate
- Zolpidem[2]
- Zopiclone
PAMs[edit]
- 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)
- Chloral hydrate,chloralose,petrichloral,and other2,2,2-trichloroethanolprodrugs
- Chlormezanone
- Clomethiazole
- Dihydroergolines(e.g.,ergoloid (dihydroergotoxine))
- Etazepine
- Etifoxine
- 2-Substitutedphenols(e.g.,thymol,eugenol)
- Imidazoles(e.g.,etomidate)
- Kavalactones(found inkava)
- Loreclezole
- Neuroactive steroids(e.g.,allopregnanolone,ganaxolone)
- Nonbenzodiazepines(e.g.,zaleplon,zolpidem,zopiclone,eszopiclone)
- Propofol
- Piperidinediones(e.g.,glutethimide,methyprylon)
- Propanidid
- Pyrazolopyridines(e.g.,etazolate)
- Quinazolinones(e.g.,methaqualone)
- Skullcapconstituents (e.g.,Baicalein)
- Stiripentol
- Disulfonylalkanes (e.g.,sulfonmethane,tetronal,trional)
- Valerianconstituents (e.g.,valeric acid,valerenic acid)
- Volatile organic compounds(e.g.,chloroform,diethyl ether,sevoflurane)
GABAB[edit]
GABABreceptorligands include:
Agonists[edit]
- 1,4-Butanediol
- Baclofen[2]
- GABA
- Gabamide
- GABOB
- gamma-Butyrolactone(GBL)
- gamma-Hydroxybutyric acid(GHB)
- gamma-Hydroxyvaleric acid(GHV)
- gamma-Valerolactone(GVL)
- Lesogaberan
- Phenibut
- 4-Fluorophenibut
- Picamilon
- Progabide
- SL-75102
- Tolgabide[2]
PAMs[edit]
GABAA-ρ[edit]
GABAA-ρ receptorligands include:
Agonists[edit]
PAMs[edit]
References[edit]
- ^Brohan J, Goudra BG (October 2017). "The Role of GABA Receptor Agonists in Anesthesia and Sedation".CNS Drugs.31(10): 845–856.doi:10.1007/s40263-017-0463-7.PMID29039138.S2CID207486777.
- ^abcdefghiGanellin CR, Triggle DJ, Macdonald F (1996).Dictionary of Pharmacological Agents.Boca Raton: Chapman & Hall/CRC. p. 608.ISBN978-0-412-46630-4.
- ^Löscher W, Rogawski MA (December 2012)."How theories evolved concerning the mechanism of action of barbiturates".Epilepsia.53(Suppl 8): 12–25.doi:10.1111/epi.12025.PMID23205959.S2CID4675696.
- ^abRuesch D, Neumann E, Wulf H, Forman SA (January 2012)."An allosteric coagonist model for propofol effects on α1β2γ2L γ-aminobutyric acid type A receptors".Anesthesiology.116(1): 47–55.doi:10.1097/aln.0b013e31823d0c36.PMC3261780.PMID22104494.
- ^Hales TG, Lambert JJ (November 1991)."The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones".British Journal of Pharmacology.104(3): 619–628.doi:10.1111/j.1476-5381.1991.tb12479.x.PMC1908220.PMID1665745.
External links[edit]
- GABA+agonistsat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
- MeSH list of agents82018755