GABA_A receptor agonist

A GABA_A receptor agonist is a drug that acts as an orthosteric agonist of the GABA_A receptor, the major signaling receptor of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).

The mechanism of action of GABA_A receptor agonists is unlike that of GABA_A positive allosteric modulators, including benzodiazepines, Z drugs, barbiturates, neurosteroids, and alcohol, which instead act via allosteric regulatory sites to potentiate GABA_A receptor function. GABA_A receptor agonists have different effects from those of GABA_A receptor positive allosteric modulators.

Examples of GABA_A receptor agonists include GABA itself, γ-amino-β-hydroxybutyric acid (GABOB), muscimol (found in Amanita muscaria mushrooms), gaboxadol (THIP), and progabide, among others. High-efficacy GABA_A receptor agonists have been found to produce sedative, hypnotic, anticonvulsant, and hallucinogenic effects, among others. The structural requirements for GABA_A receptor binding and activation have been found to be very strict, so relatively few high-efficacy GABA_A receptor agonists are known. No fully selective GABA_A receptor agonists, for instance lacking any additional activity at the closely related GABA_A-ρ and/or GABA_B receptors, are currently known.

GABA_A receptor agonists are generally GABA analogues and derivatives. Muscimol, a conformationally restrained analogue of GABA, was among the first GABA_A receptor agonists to be identified.