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Abstract

We sought to determine whether the clinically effective anticonvulsant drug valproate exhibited antiepileptogenic properties in the kindling model (we use the term anticonvulsant to mean suppression of seizure, and antiepileptogenic to mean suppression of development of epilepsy). We compared and contrasted valproate with two other anticonvulsan drugs, phenobarbital and carbamazepine. We investigated the effects of these drugs on the development of kindling that is, the number of stimulation-induced afterdischarges required to induce enhanced seizure susceptibility in rats Valproate exhibited powerful antiepileptogenic effects as evident in a dose-dependent increase in the number of afterdischarges required to induce kindling. These effects were not due to retained valproate or an active metabolite merely masking the expression of kindled seizures. By contrast, carbamazepine was devoid of any antiepileptogenic effects despite exhibiting marked anticonvulsant effects. Like valproate, phenobarbital exhibited both antiepileptogenic and anticonvulsant properties, but its antiepileptogenic properties were significantly less pronounced. The antiepileptogenic effects of valproate and phenobarbital strengthen the candidacy of these agents for the clinical studies needed to investigate pharmacological prevention of the development of epilepsy in high-risk groups.