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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]
The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes (non-neuronal glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA. [2]
Glutamate is a very major constituent of a wide variety of proteins; consequently it is one of the most abundant amino acids in the human body. [1] Glutamate is formally classified as a non-essential amino acid, because it can be synthesized (in sufficient quantities for health) from α-ketoglutaric acid, which is produced as part of the citric acid cycle by a series of reactions whose ...
[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.
[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 is also the primary inhibitory neurotransmitter in the cerebral cortex and has the highest level of expression within it. [15] The GABA affinity (K m) of the mouse isoform of GAT1 is 8 μM. [16] In the brain of a mature mammal, glutamate is converted to GABA by the enzyme glutamate decarboxylase (GAD) along with the addition of vitamin B6.
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.
Besides giving GABA receptors an extra inhibitory punch, alcohol substrates bind to glutamate receptors, which blocks its excitatory activity. Alcohol effects on both of these metabolic pathways obstruct the brain from making memories, making well thought out decisions, and controlling impulses after long term use.