Single systemic dose of vigabatrin induces early proconvulsant and later anticonvulsant effect in rats

Vigabatrin (VGB), an inhibitor of gamma-aminobutyric acid-aminotransferase, exhibits an antiepileptic effect but several studies indicate that its effect may be biphasic. A time course of an effect of a single injection of VGB on hippocampal epileptic afterdischarges (AD) elicited by an electric stimulation of the angular bundle was examined in adult rats with chronically implanted electrodes. VGB (600 or 1200 mg/kg intraperitoneally) proved to be an efficient anticonvulsant in the intervals of 24 and 48 h--duration of ADs was shortened and behavioral phenomena were less intense. In contrast, ADs were lengthened 4 h after administration. The biphasic effect of VGB was demonstrated, the initial proconvulsant effect might be due to a different onset of VGB action in individual brain structures, but an additional mechanism of action cannot be excluded.