Drug effects on afterdischarge and seizure threshold in lissencephalic ferrets: an epilepsy model for drug evaluation.

In normal and lissencephalic ferrets with chronically implanted electrodes, two antiepileptic drugs, (E)-2-[(amino)phenylmethylen]-benzo [b] thiophen-3(2H)-on (AF-CX 921 XX) and carbamazepine (CBZ), were compared. The variables included afterdischarges (AD) and seizures induced by cortical electrical stimulations (ES). Both drugs were given orally, 100 mg/kg of pure substance. ES was applied before and 1, 2, 3, 4, 5, and 24 h after drug administration. Lissencephaly was produced by a single intraperitoneal injection of 15 mg methylazoxymethanol acetate to pregnant animals. The administration of both drugs resulted in increases of the AD threshold current to 240% in the normal and to 170% in the lissencephalic ferrets, in comparison with control stimulations (the difference significant at p less than 0.001). Moreover, duration of the AD was shorter (p less than 0.01) than before the drugs. Seizure threshold also increased 170% after AF-CX 921 XX and 175% after CBZ in normal and 153% and 138% in lissencephalic ferrets, respectively. The difference between the two drugs was significant. However, in contrast to the threshold, duration of seizures during AF-CX 921 XX administration was significantly shorter (p less than 0.05) than during CBZ. In general, lissencephalic ferrets responded less than normal ferrets to both drugs, but AF-CX 921 XX had a greater inhibitory effect on the duration of seizures. The lissencephalic ferret is proposed as an animal model of epilepsy with diffuse developmental defects.