Conventional anticonvulsant drugs in the guinea-pig kindling model of partial seizures: effects of repeated administration

Abstract

This study addressed the anticonvulsant effects of repeated administration of phenytoin, carbamazepine, phenobarbital, valproate, and ethosuximide in kindled guinea-pigs in order to further substantiate this novel model of partial seizures for the screening of future anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using scores on a sedation/muscle relaxation rating index. In response to suprathreshold stimulation, the anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge duration (ADD) and behavioral seizure severity (SS) during a repeated drug treatment schedule in kindled guinea-pigs. All drugs exerted slight to moderate sedative effects in guinea-pigs on our rating index. We found that phenytoin, carbamazepine, and phenobarbital exhibited effective anticonvulsant properties in kindled guinea-pigs by reducing both ADD and SS. We found that valproate consistently reduced ADD throughout the treatment schedule but failed to significantly reduce SS. Lastly, ethosuximide failed to exhibit effective anticonvulsant properties. Our results indicate that the guinea-pig kindling model correctly predicted the actions of these common anticonvulsant drugs in the treatment of partial seizures. Guinea-pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.