Vigabatrin was specifically designed to enhance γ-aminobutyric acid (GABA) function in the CNS. By increasing brain concentrations of this inhibitory neurotransmitter the drug appears to decrease propagation of abnormal hypersynchronous discharges, thereby reducing seizure activity.

At this stage in its development, clinical experience with vigabatrin is limited primarily to patients with refractory seizure disorders. In this difficult-to-treat population, ‘add-on’ therapy with vigabatrin ⩾ 2 g/day has shown impressive efficacy, reducing seizure frequency by ⩾ 50% in approximately half of patients. Clinical efficacy does seem to vary with seizure type with the best response reported in adults with complex partial seizures with or without generalisation and in children with cryptogenic partial epilepsy or symptomatic infantile spasm. Vigabatrin appears to have a negative effect on absences and myoclonic seizures.

Some disorders of motor control may also be amenable to enhanced GABAergic function. In the small number of patients with tardive dyskinesia treated to date, vigabatrin produced mild to moderate improvement in hyperkinetic symptom scores but Parkinsonism or schizophrenic symptoms occasionally worsened. The best response was reported in a study of patients who had been withdrawn from neuroleptic therapy. In a small but well-controlled comparative trial, vigabatrin was as effective as baclofen in reducing spasm and improving some parameters of spasticity in patients with spinal cord lesions or multiple sclerosis.

Most adverse reactions to vigabatrin are mild and transient with central nervous system (CNS) changes being reported most frequently. Of particular note, serial evoked potential studies and the few available histology reports have not found evidence of intramyelinic oedema during therapeutic use, as was reported in rats and dogs on chronic high-dose treatment.

Thus, vigabatrin is a promising new anticonvulsant drug. Current evidence supports a trial of this agent as adjunctive therapy in patients with refractory seizure disorders, and future investigation of vigabatrin monotherapy and its efficacy relative to established agents is awaited with interest. Wider experience should help to clarify which patients — by seizure type and concurrent CNS pathology — are likely to benefit from vigabatrin and ongoing monitoring should further clarify the potential detrimental effects, if any, of long term use. In the meantime, it is a welcome addition in the difficult setting of resistant epilepsy.

Vigabatrin was specifically designed to increase brain GABA levels by inhibiting catabolism of this neurotransmitter. It replaces GABA as substrate for GABA transaminase (GABA-T), but enzymatic activation produces an intermediate which binds covalently to the active site, thereby consuming both enzyme and inhibitor in an irreversible reaction. Only the S(+)-enantiomer of vigabatrin is pharmacologically active.

In vitro the effect on other enzymes is very minor and, in particular, vigabatrin does not inhibit GABA synthesis via glutamate decarboxylase (GAD). In v/vo, however, GAD activity is significantly decreased after repetitive dosing in rodents, which is perhaps related to feedback inhibition from the very high levels of GABA. Exposure of cultured mouse neurons to 10 μmol/ L of vigabatrin resulted in a 3.5-fold increase in GABA content. After withdrawal of the drug from culture, GABA-T activity returned to pre-exposure levels after 4 to 6 days, reflecting the time required to synthesise new enzyme. S-vigabatrin is …