A comparative study of the effects of phenytoin and phenobarbital on electrically induced maximal seizures in frogs and mice

This study was undertaken to compare seizure patterns and anticonvulsant effects of phenytoin in frogs (Rana pipiens) and the CF-1 strain of mice. Maximal seizures were induced with electroshock via corneal electrodes, and phenytoin anticonvulsant effects were determined by measuring the duration of tonic hindlimb extension (THE) and prevention of the THE. To control for any possible species difference that might be unique to phenytoin, the anticonvulsant effects of phenobarbital also were compared in frogs and mice. It was found that the dose-effect relationships for shortening THE duration and for prevention of THE by phenobarbital in frogs and mice were not significantly different in terms of slopes and potencies. With phenytoin, however, the dose-effect relationship for prevention of THE in mice was significantly steeper than that in frogs, whereas the slopes of the dose-effect relationships for shortening THE duration were not significantly different in these two species. Frogs decapitated 1.5 sec after electroshock exhibited THE durations equal to those in intact frogs, and phenytoin and phenobarbital efficacies in shortening THE duration were unchanged by decapitation. These results show that shortening of THE duration by both phenytoin and phenobarbital may reflect drug action in spinal or peripheral neural pathways. Also, it is suggested that phenytoin, but not phenobarbital, prevents THE by a selective action on cortical structures which are well developed in mice but are poorly developed or absent in frogs.