Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
which in humans is encoded by the ''GABRA5''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at
GABAA receptors, which are
ligand-gated
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
chloride channel
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Several ...
s. Chloride conductance of these channels can be modulated by agents such as
benzodiazepines that bind to the GABA
A receptor. At least 16 distinct subunits of GABA
A receptors have been identified. Transcript variants utilizing three different alternative non-coding first
exons have been described.
Subunit selective ligands
Recent research has produced several ligands which are moderately selective for GABA
A receptors containing the α
5 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
In neurology, anterograde amnesia is the inability to create new memories after the event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact ...
. Inverse agonists at this subunit have
nootropic
Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic dietary supplement, supplements or drugs and other substances that are claimed to improve cognitive function ...
effects and may be useful for the treatment of cognitive disorders such as
Alzheimer's disease.
Agonists
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QH-ii-066
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SH-053-R-CH3-2′F
Antagonists
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α5IA
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Basmisanil (RG-1662, RO5186582): derivative of Ro4938581, negative allosteric modulator at GABA
A α
5, in human trials for treating cognitive deficit in
Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
.
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L-655,708
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MRK-016
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PWZ-029: moderate inverse agonist
*
Pyridazine
Pyridazine is an aromatic, heterocyclic, organic compound with the molecular formula . It contains a six-membered ring with two adjacent nitrogen atoms. It is a colorless liquid with a boiling point of 208 °C. It is isomeric with two other ...
s
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Ro4938581
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TB-21007
See also
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GABAA receptor
References
Further reading
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External links
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Ion channels
Biology of bipolar disorder
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