4-aminobutyrate aminotransferase (ABAT) and voltage-gated sodium channels (VGSC) (ABAT and VGSC)

This target profile represents a combination of two distinct protein classes: the enzyme 4-aminobutyrate aminotransferase (GABA transaminase) and the family of voltage-gated sodium channels. GABA transaminase is a mitochondrial, pyridoxal phosphate-dependent enzyme responsible for the degradation of GABA, the primary inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde (1). Voltage-gated sodium channels are transmembrane proteins that facilitate the rapid influx of sodium ions, which is essential for the initiation and propagation of action potentials in neurons (2). Drugs that interact with both targets, most notably valproic acid, achieve therapeutic effects by increasing synaptic GABA concentrations and limiting high-frequency repetitive neuronal firing (3). This dual mechanism is highly effective in stabilizing hyperexcitable neuronal networks, making it a primary strategy for treating epilepsy, bipolar disorder, and neuropathic pain (4). However, the broad systemic impact of modulating these targets necessitates careful monitoring for adverse effects such as hepatotoxicity and teratogenicity (5).

Other names

GABA transaminase and voltage-gated sodium channelsGABA-T and VGSCABAT and Sodium channels4-aminobutyrate aminotransferase and voltage-gated sodium channels

Inhibition of 4-aminobutyrate aminotransferase leads to increased concentrations of the inhibitory neurotransmitter GABA, while the blockade of voltage-gated sodium channels prevents the sustained high-frequency repetitive firing of action potentials.