Effects of valproate, phenytoin, and zonisamide on clonic and tonic seizures induced by acute and repeated exposure of mice to flurothyl.

The effects of valproate (VPA), zonisamide (ZNS), and phenytoin (PHT) on flurothyl (FE)-induced generalized seizure were investigated in mice. In the FE kindling model, eight daily FE-induced generalized clonic seizures followed by a 28-day stimulation-free interval converted the type of seizure expressed in response to FE from clonic to tonic. In an acute FE trial experiment, the latencies of clonic and tonic seizures were prolonged significantly and dose-dependently by the administration of VPA. ZNS and PHT did not show any effect on the latencies of tonic seizure. When the same three drugs were administered to mice daily for 8 days prior to the FE trial, changes in the seizure phenotypes from clonic to tonic seizure were significantly inhibited by VPA and ZNS, but not by PHT. These results suggest that VPA and ZNS possess significant antiepileptogenic properties. PHT apparently does not share this property to the same degree in the present FE-induced model.