Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene. [5] [6]
Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene. [5] [6]
GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described. [5]
Recent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amnesia. Inverse agonists at this subunit have nootropic effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease.
Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene.
Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.
Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the GABRB3 gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation.
Gamma-aminobutyric acid receptor subunit beta-1 is a protein that in humans is encoded by the GABRB1 gene.
Gamma-aminobutyric acid receptor subunit rho-1 is a protein that in humans is encoded by the GABRR1 gene.
Gamma-aminobutyric acid receptor subunit alpha-6 is a protein that in humans is encoded by the GABRA6 gene.
Gamma-aminobutyric acid receptor subunit alpha-3 is a protein that in humans is encoded by the GABRA3 gene.
Gamma-aminobutyric acid receptor subunit alpha-2 is a protein in humans that is encoded by the GABRA2 gene.
Gamma-aminobutyric acid receptor subunit epsilon is a protein that in humans is encoded by the GABRE gene.
Gamma-aminobutyric acid receptor subunit alpha-4 is a protein that in humans is encoded by the GABRA4 gene.
Gamma-aminobutyric acid receptor subunit rho-2 is a protein that in humans is encoded by the GABRR2 gene.
GABAA receptor-γ3, also known as GABRG3, is a protein which in humans is encoded by the GABRG3 gene.
Gamma-aminobutyric acid receptor subunit delta is a protein that in humans is encoded by the GABRD gene. In the mammalian brain, the delta (δ) subunit forms specific GABAA receptor subtypes by co-assembly leading to δ subunit containing GABAA receptors.
Gamma-aminobutyric acid receptor subunit pi is a protein that in humans is encoded by the GABRP gene.
Gamma-aminobutyric acid receptor subunit gamma-1 is a protein that in humans is encoded by the GABRG1 gene. The protein encoded by this gene is a subunit of the GABAA receptor.
Gamma-aminobutyric acid receptor subunit theta is a protein that in humans is encoded by the GABRQ gene. The protein encoded by this gene is a subunit of the GABAA receptor.
Gamma-aminobutyric acid receptor subunit rho-3 is a protein that in humans is encoded by the GABRR3 gene. The protein encoded by this gene is a subunit of the GABAA-ρ receptor.
TPA-023 (MK-0777) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. It is a subtype-selective, mixed allosteric modular at the benzodiazepine location on GABAA receptors, where it acts as a partial agonist at the α2 and α3 subtypes, but as a silent antagonist at α1 and α5 subtypes. It has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose.
α5IA (LS-193,268) is a nootropic drug invented in 2004 by a team working for Merck, Sharp and Dohme, which acts as a subtype-selective inverse agonist at the benzodiazepine binding site on the GABAA receptor. It binds to the α1, α2, α3 and α5 subtypes.
L-655,708 (FG-8094) is a nootropic drug invented in 1996 by a team working for Merck, Sharp and Dohme, that was the first compound developed which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. It acts as an inverse agonist at the α1, α2, α3 and α5 subtypes, but with much higher affinity for α5, and unlike newer α5 inverse agonists such as α5IA, L-655,708 exerts its subtype selectivity purely via higher binding affinity for this receptor subtype, with its efficacy as an inverse agonist being around the same at all the subtypes it binds to.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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