Effect of anticonvulsants on seizures developing in the course of daily administration of pentetrazol to rats.

Progressive behavioral and electroencephalographic (EEG) changes were examined following daily administration of pentetrazol (PTZ) to rats. A dose (40 mg/kg/day i.p.) of PTZ which, on the first day, induced clonic convulsions with spike and wave complexes, over several days progressively increased its effect and finally induced 'violent convulsions' with EEG seizures of high frequency components. In rats showing these violent convulsions, the PTZ convulsive threshold was decreased and, even after a 4- to 10-month resting period, the violent convulsion was elicited with the same dose of PTZ. Trimethadione and phenobarbital in doses blocking clonic convulsion in normal rats, did not suppress these violent convulsions. Higher doses of the two drugs were necessary to suppress the violent convulsion. Diphenylhydantoin did not suppress either type of convulsions. It is suggested that the progressive development of seizure by PTZ is a kindling effect and that a part of the neuronal mechanisms by which the violent convulsion occurs is involved in the mechanisms underlying the clonic convulsion.