Acute effects of vigabatrin on brain GABA and homocarnosine in patients with complex partial seizures

Abstract

Purpose: The acute, subacute, and chronic effects of vigabatrin (VGB) were studied in patients with refractory complex partial seizures. VGB increases human brain gamma-aminobutyric acid (GABA) and the related metabolites, homocarnosine and 2-pyrrolidinone.

Methods: In vivo measurements of GABA and homocarnosine were made of a 14-cc volume in the occipital cortex by using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Six patients (three women) were studied serially during the initiation and maintenance of VGB as adjunct therapy.

Results: The first, 3 g dose of VGB increased brain GABA by 2.0 micromol/g within 81 min of oral administration. After 2 h, median edited GABA remained essentially the same for 2 days. The response to the second, 3-g dose of VGB given at 48 h was considerably less than that to the first dose, with a median increase of 0.5 micromol/g within 72 min. After 2-3 months, rechallenging patients taking 1.5-g VGB twice daily with 6 g increased GABA by 0.4 micromol/g within 87 min. Homocarnosine increased more gradually than GABA to above-normal levels after a week of VGB therapy.

Conclusions: VGB promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Once-a-day dosing is sufficient to increase GABA. Patients may be expected to experience the effects of increased homocarnosine within 1 week.