The author assessed anticonvulsive effects of sulthiame(SUL) on the amygdaloid(AM) kindled seizure in rats, which has been used as a model of temporal lobe epilepsy with secondary generalization and as a suitable seizure model for pharmacological testing.
Tripolar electrodes were implanted into the left AM of adult male Wistar rats. The animals were kindled at the afterdischarge(AD) threshold. After completion of kindling, generalized seizure triggering threshold was determined. The drugs or control vehicles (polythylene glycol 400) were administered intraperitoneally only in rats that stably reproduced generalized convulsions at the near-threshold stimulation. In experiment I, single administration of SUL was done with doses of 25㎎/㎏, 50㎎/㎏, 100㎎/㎏ and 200㎎/㎏ of body weight at a volume of 1㎖/㎏. In experiment Ⅱ, animals were divided into 3 groups; group 1 for SUL 50㎎/㎏, group 2 for SUL 200㎎/㎏ and group 3 for control trials.
The drugs or vehicles were administered once daily for 8 consecutive days. In both experiments, kindled seizure satge was observed, and duratin of forelimb clonus(FCL) and duration of AD on electroencephalography(EEG) were monitored.
Single administration of SUL(n=7-9) reduced FCL duration of final stage seizures, and only the highest dose significantly regressed secondary generalization. During 8 days repeated administration of SUL 50㎎/㎏(n=6), FCL duration was sinificantly alleviated until the 5th day of treatment. With the dose of 200㎎/㎏(n=6), on the other hand, significant suppression of secondary generalization was noted only until the 2nd test day, but significant reductions of FCL and AD duration of the final stage seizures were preserved afterwards.
The anticonvulsive effects of SUL indicated in the present study were not comparable to those of conventional antiepileptic drugs(AEDs) such as carbamazepine, phenytoin, phenobarbital, zonisamide and topiramate reported previously and were rather different from those of acetazolamide which only alleviated the FCL and AD duration without significant regression of secondary generalized seizure even at higher doses, but the difference was noted only transiently.
Based on the present study and previous studies with the same methodology, pharmacological test using kindling model is thought to be an useful method for not only characterizing the clinical pharmacological effects of AEDs, but also better understanding of their action mechanisms.
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