ANTICONVULSANT ACTIVITY OF TOPIRAMATE AND PHENYTOIN IN A RAT MODEL OFISCHEMIA-INDUCED EPILEPSY

Topiramate, a structurally novel anticonvulsant, and phenytoin were ev aluated in a rat model of ischemia-induced epilepsy. In this model a t ransient global cerebral ischemia is induced by cardiac compression. B y precisely controlling the experimental conditions the procedure caus es reproducible neurological deficits that include audiogenic epilepti c seizures. The seizures can be broadly separated into three types ref lecting the degree of severity: wild running, clonic seizures, and ton ic extension seizures of the forelimbs and hindlimbs. Topiramate and p henytoin blocked all three types of seizures. Calculated ED(50) values for topiramate 1 hr after oral administration were 8.2, 13.0 and 36.1 mg/kg for blockade of tonic extension seizures, clonic seizures and w ild running, respectively. Corresponding ED(50) values for phenytoin w ere 5.0, 10.8 and 20.7 mg/kg. These results support the concept that t he anticonvulsant activity of these drugs is due primarily to an abili ty to block the spread of seizures.