Γ-aminobutyric acid in the context of "Muscimol"

The GABA_A receptor (GABA_AR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Accurate regulation of GABAergic transmission through appropriate developmental processes, specificity to neural cell types, and responsiveness to activity is crucial for the proper functioning of nearly all aspects of the central nervous system (CNS).Upon opening, the GABA_A receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl
) and, to a lesser extent, bicarbonate ions (HCO
₃).

GABA_AR are members of the ligand-gated ion channel receptor superfamily, which is a chloride channel family with a dozen or more heterotetrametric subtypes and 19 distinct subunits. These subtypes have distinct brain regional and subcellular localization, age-dependent expression, and the ability to undergo plastic alterations in response to experience, including drug exposure.

Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) and by its former developmental code names Lu-2-030, MK-0928, and OV101, is a GABA_A receptor agonist related to muscimol which was investigated for the treatment of insomnia and other conditions like Angelman syndrome but was never marketed. At lower doses, the drug has sedative and hypnotic effects, and at higher doses, it produces hallucinogenic effects. It is taken orally.

The drug acts as a potent and selective partial agonist of the GABA_A receptor, the major signaling receptor of the inhibitory endogenous neurotransmitter γ-aminobutyric acid (GABA). However, it acts as a preferential supra-maximal agonist at extrasynaptic δ subunit-containing GABA_A receptors. In contrast to GABA_A receptor positive allosteric modulators like benzodiazepines and Z drugs, gaboxadol is an orthosteric agonist of the GABA_A receptor, acting on the same site as GABA rather than at an allosteric regulatory site. As a result, gaboxadol has differing effects from benzodiazepines and related drugs. Gaboxadol is a conformationally constrained synthetic analogue of GABA and of muscimol, an alkaloid and hallucinogen found in Amanita muscaria (fly agaric) mushrooms. It has greatly improved drug-like properties compared to these compounds.