Antiepileptic drug evaluation in a new animal model: spontaneous petit mal epilepsy in the rat.
One-third of Wistar rats bred in our laboratory present recurrent seizures whose EEG and clinical symptomatology resemble those of human petit mal. Bilateral cortical synchronous spike- and wave discharges (7-11 c/s; 200-600 microV, lasting 0.5 to 40 s) accompany behavioral arrest and are associated frequently with facial myoclonia. These seizures, observed as long as the animals survive, appear spontaneously and seem to be unrelated to surgical procedures. Antiepileptics in common clinical use were tested. Ethosuximide (greater than 12.5 mg/kg), diazepam (greater than 0.5 mg/kg), trimethadione and sodium valproate (greater than 50 mg/kg) suppressed these discharges in a dose related manner. Carbamazepine and phenytoin were ineffective or aggravated the seizures. Phenobarbital, effective at 2.5 to 10 mg/kg, was ineffective at 20 mg/kg. The similar effects of these antiepileptics on both the rats' seizures and human petit mal confirm the hypothesis that this phenomenon constitutes a valid pharmacological model of petit mal epilepsy. Its predictive value appears to be superior to that of other currently used models.
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000503:physiopathology; D005013:Ethosuximide / Q000627:therapeutic use; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014293:Trimethadione / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
D000927:Anticonvulsants; D002220:Carbamazepine; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin; D003975:Diazepam; D014293:Trimethadione; D010634:Phenobarbital