The convulsant effects of four doses of picrotoxin (PX) - 2, 3, 4, and 6 mg/kg s.c. - were evaluated in the first part of the study. The 4- mg/kg dose, which elicited minimal seizures in all animals, generalized tonic-clonic (major) seizures in 75 % of rats and fatal outcome in 69 % of rats, was chosen for the second part, i.e. for testing the anticonvulsant action of clonazepam (Rivotril1* Roche, 0.1 or 1 mg/kg i.p.). Clonazepam exhibited a dose-dependent action against PX-induccd seizures, being more efficient against major than against minimal seizures.
The action of ethosuximide, valproate and clonazepam against pentylenetetrazol-induced epileptic EEG phenomena was studied in acute experiments in rats with intercollicular brainstem transection. Ethosuximide lost its action against both rhythmic metrazol activity (model of human absences) and EEG seizures. On the contrary, the action of valproate and clonazepam in cerveau isolé rats was the same as in intact animals. The site of anticonvulsant action of ethosuximide may be localized in hindbrain structures, whereas the actions of both valproate and clonazepam may be demonstrated even if hindbrain structures had been eliminated.