GammaAminobutyric

Gamma-aminobutyric acid, commonly abbreviated as GABA, is the principal inhibitory neurotransmitter in the vertebrate central nervous system. It is synthesized from glutamate by the enzyme glutamate decarboxylase (GAD) with pyridoxal phosphate (vitamin B6) as a cofactor. In humans, two GAD isoforms—GAD65 and GAD67—support GABA production in neurons. GABA is released at inhibitory synapses and binds to postsynaptic receptors to dampen neuronal excitability.

GABA activity is terminated primarily by reuptake into neurons and glia through GABA transporters (GATs), especially GAT-1. It is then metabolized by GABA transaminase (GABA-T) to succinic semialdehyde, which is further converted to succinate and enters the tricarboxylic acid cycle. This recycling and metabolism maintain inhibitory signaling in neural circuits.

GABA exerts its effects through three classes of receptors: GABA-A (ionotropic chloride channels), GABA-B (metabotropic G protein–coupled receptors), and GABA-C (also known as GABA-A rho, a distinct ionotropic receptor). GABA-A receptors mediate fast inhibitory synaptic currents and are targeted by benzodiazepines, barbiturates, and various anesthetics. GABA-B receptors are involved in slower, longer-lasting inhibition and modulate neurotransmitter release. GABA-A rho receptors contribute to inhibitory signaling in specific pathways.

Pharmacologically, enhancing GABAergic signaling is a strategy for treating epilepsy, anxiety disorders, insomnia, and spasticity. Drugs include GABA reuptake inhibitors, GABA-T inhibitors, and GABA receptor agonists or positive allosteric modulators; some anticonvulsants and sedatives act via these mechanisms. Deficits in GABAergic transmission are linked to increased neural excitability observed in epilepsy and related conditions.

GABA was identified in the brain during the 1950s as a neurotransmitter and has since been recognized as a central regulator of inhibitory synaptic transmission.