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In this study, we compared the anticonvulsive effects of zonisamide (ZNS) with those of phenytoin (PHT), carbamazepine (CBZ) and phenobarbital (PB) in amygdaloid (AM)-kindled rats. Electrodes were implanted into the left AM of adult male Wistar rats. The animals were kindled at the afterdischarge (AD) threshold. After the completion of kindling, the generalized seizure triggering threshold was determined. The drugs were administered intraperitoneally in animals that showed stable generalized convulsions at near-threshold stimulation. Immediately after each drug trial, venous blood was sampled and the serum drug concentration was measured using EMIT or HPLC. All the drugs suppressed secondary generalization at lower doses, and further regressed the seizure stage and reduced the AD duration at higher doses. Higher doses of all drugs except ZNS, however, produced motor ataxia or lethargy. Thus, ZNS seemed to have a wider therapeutic range than other conventional antiepileptic drugs. An additional experiment on the effects of ZNS against supra-threshold stimulation suggested that a major action of ZNS in the kindling model is to attenuate the seizure spread rather than to elevate the AD threshold at the focus.
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Reference:
Benzisoxazole – Wikipedia,
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