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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]
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 .
In pharmacology, GABA A receptor positive allosteric modulators, also known as GABAkines or GABA A receptor potentiators, [1] are positive allosteric modulator (PAM) molecules that increase the activity of the GABA A receptor protein in the vertebrate central nervous system. GABA is a major inhibitory neurotransmitter in the central nervous system.
[9] [10] Because GABA-T degrades GABA, the inhibition of this enzyme has been the target of many medical studies. [9] The goal of these studies is to find a way to inhibit GABA-T activity, which would reduce the rate that GABA and 2-oxoglutarate are converted to semialdehyde and L-glutamate, thus raising GABA concentration in the brain.
GABA receptor antagonists are drugs that inhibit the action of GABA. In general these drugs produce stimulant and convulsant effects, and are mainly used for counteracting overdoses of sedative drugs. Examples include bicuculline, securinine and metrazol, and the benzodiazepine GABA A receptor antagonist flumazenil.
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[36] [37] [38] Although the term "GABA С receptor" is frequently used, GABA С may be viewed as a variant within the GABA A receptor family. [7] Others have argued that the differences between GABA С and GABA A receptors are large enough to justify maintaining the distinction between these two subclasses of GABA receptors.