Anticonvulsant profile of flunarizine

The purpose of the study was to examine in a multi-experimental profile the purported similarity between the anticonvulsant effects of flunarizine, diphenylhydantoin, and carbamazepine. The compounds were injected at different time intervals and by different routes, and their effects were examined in a genetic model of epilepsy (audiogenic seizures in mice), against maximal seizures induced by bicuculline in mice and rats and in a seizurethreshold test (bicuculline infusion) in rats. All three compounds primarily affected tonic seizures. In the bicuculline seizure test, this was an all-or-none effect. In this test, flunarizine differed from diphenylhydantoin and carbamazepine in that it increased the threshold for clonic-hindpaw seizures. Thus, flunarizine, apart from antagonizing tonic seizures, also increased the threshold for generalization. Further, in agreement with previous experiments (maximal metrazol test and kindling), the duration of action of flunarizine is longer than that of diphenylhydantoin and carbamazepine. Finally, the degree of ataxia and neurological deficits caused by a high p.o. dosis of flunarizine was assessed. A slight neurological deficit and ataxia occurred 1 hr after p.o. administration of 160 mg/kg of flunarizine. By way of analogy with diphenylhydantoin, as a working hypothesis, it is suggested that the anticonvulsant actions of flunarizine result from reducing Na+ currents in neurons, although a direct effect on Ca2+ movements cannot be excluded.