GABA T-2 Inhibitors

GABA T-2 inhibitors are chemicals with the shared characteristic of interfering with the activity of GABA Transaminase 2, an enzyme crucial for the catabolism of the neurotransmitter GABA. Vigabatrin and Gabaculine, for instance, act directly on GABA T-2. Vigabatrin forms an irreversible bond with the enzyme, it from converting GABA to succinic semialdehyde. Gabaculine acts by forming a covalent bond with pyridoxal phosphate (PLP) in the enzyme's active site. Other inhibitors act indirectly by affecting pathways that eventually modulate the activity or levels of GABA T-2. Phenelzine, an MAO inhibitor, inhibits the degradation of GABA, thereby affecting GABA T-2 indirectly. Similarly, Valproic Acid inhibits GABA transaminase, contributing to elevated GABA levels that inhibit GABA T-2. A distinct subgroup of GABA T-2 inhibitors acts by modulating ion channels or neurotransmitter receptors that indirectly influence GABA T-2. For example, Lamotrigine modulates voltage-gated sodium channels and stabilizes neuronal membranes, enhancing GABA availability. Riluzole inhibits both sodium channels and glutamate release, ultimately affecting GABA T-2 by stabilizing cellular excitability. Baclofen, a GABA(B) receptor agonist, and Muscimol, a GABA(A) receptor agonist, further contribute to modulating GABA T-2 by affecting the receptors that in turn influence GABA levels and its catabolism. These chemicals showcase the intricate network of biochemical pathways that can be manipulated to modulate GABA T-2 activity.