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A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to increased extracellular concentrations of GABA and therefore an increase in GABAergic neurotransmission. [1]
By the early 1970s, it was appreciated that there are two main classes of GABA receptors, GABA A and GABA B and also that baclofen was an agonist of GABA B receptors. Gabapentin was designed, synthesized and tested in mice by researchers at the pharmaceutical company Goedecke AG in Freiburg, Germany (a subsidiary of Parke-Davis ).
The gabapentinoids are 3-substituted derivatives of GABA; hence, they are GABA analogues, as well as γ-amino acids. [3] [4] Specifically, pregabalin is (S)-(+)-3-isobutyl-GABA, phenibut is 3-phenyl-GABA, [28] and gabapentin is a derivative of GABA with a cyclohexane ring at the 3 position (or, somewhat inappropriately named, 3-cyclohexyl-GABA).
Inhibition of GABA transaminase enzymes reduces the degradation of GABA, leading to increased neuronal GABA concentrations. Examples include valproic acid , [ 2 ] vigabatrin , [ 3 ] [ 4 ] phenylethylidenehydrazine (and drugs that metabolize to it, such as phenelzine [ 5 ] ), ethanolamine- O -sulfate (EOS), and L- cycloserine .
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Gamma-aminobutyric acid, a GABA-B receptor agonist. A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. [1] There are three receptors of the gamma-aminobutyric acid. The ...
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