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 eff ect may be biphasic. A time course of an effect of a single injection of VG B on hippocampal epileptic afterdischarges (AD) elicited by an electric sti mulation of the angular bundle was examined in adult rats with chronically implanted electrodes. VGB (600 or 1200 mg/kg intraperitoneally) proved to b e 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 w as demonstrated, the initial proconvulsant effect might be due to a differe nt onset of VGB action in individual brain structures, but an additional me chanism of action cannot be excluded. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.