Anticonvulsant effects of chronic treatment with phenytoin against pentylenetetrazole-induced seizures in the mouse.

Acute administration of phenytoin (40 and 75 mg/kg) was unable to counteract seizures induced by pentylenetetrazole and even prolonged them in some cases. These prolonged seizures remained with chronic (10 days) treatment but an anticonvulsant effect of phenytoin (40 and 75 mg/kg) also emerged, shown by a decrease in the incidence of seizures. This latter effect could be detected even 24 hr after the last dose. Both acute and chronic treatment with phenytoin (40 or 75 mg/kg) were able to enhance anticonvulsant efficacy of diazepam against pentylenetetrazole-induced seizures. The mechanisms underlying these three independent effects of phenytoin and their clinical relevance are discussed.