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Vigabatrin is an antiepileptic drug that inhibits the catabolism of gamma-aminobutyric acid (GABA) by irreversibly inhibiting GABA transaminase.

GABAergic synapses comprise approximately 30% of all synapses within the central nervous system, and therein underlies the primary mode of synaptic inhibition. Unlike many CNS-related drugs that have been discovered through serendipity, vigabatrin was rationally constructed to have a precise effect on brain chemistry. Specifically, vigabatrin was designed to be an enzyme-activated, irreversible, selective suicide inhibitor of GABA transaminase.

The effect of vigabatrin is the inhibition of GABA catabolism by GABA transaminase, leading to an increase in GABA available in the synaptic cleft, thereby resulting in enhanced GABAergic transmission. The increase in GABA functions as a brake on the excitatory processes that can initiate seizure activity.

Despite the short half-life of vigabatrin in the body (5-7 h) and its relatively low concentration in cerebrospinal fluid (10% of the concentration observed in plasma), it has the profound effect of increasing GABA concentration in the brain for more than a week after a single dose in humans. This effect persists steadily over years of vigabatrin administration and results in significant and persistent decreases in seizure activity. Vigabatrin can be effective with once-daily dosing. Because of its specificity, vigabatrin has helped researchers explore the specific mechanisms within the brain that underlie seizure activity.

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