DEVELOPMENT OF NEW ANTIEPILEPTIC DRUG FROM BIOTOXIN WITH EFFECT ON NON-NMDARECEPTOR

为了明确JORO蜘蛛毒素类似物1-萘基乙酰精胺（1-NA-Spm）对某些癫痫模型具有抗惊厥作用，我们采用ampa致痫和点燃动物模型。环噻嗪类药物作为变构调节剂作用于AMPA受体。体内研究表明，环噻嗪通过降低脱敏来增强AMPA受体介导的电流。在这项研究中，环噻嗪以剂量依赖的方式增强了ampa诱导的惊厥发作，并引起CA3/4锥体细胞的广泛损失。预处理1-NA-Spm抑制环噻嗪增强ampa诱导的惊厥发作和锥体细胞变性。在杏仁核点燃的动物中，1-NA-Spm剂量依赖性地改善了癫痫发作，并缩短了给药后30分钟的放电时间。抗惊厥作用在给药1天后仍有，4天后逐渐消失。本研究结果表明，1-NA-Spm是一种有效的长效抗惊厥药，可能成为新型抗癫痫药物的候选药物。

In order to clear that 1-naphtyl acetyl spermine (1-NA-Spm), an analogue of JORO spider toxin, has anticonvulsant effect on some epileptic models, we used the model of AMPA-induced seizure and kindled animals.It has been known that cyclothiazide affect AMPA receptors as allosteric modulator. In vivo studies showed that cyclothiazide potentiated AMPA receptor mediated current by decreasing desensitization. In this study, cyclothiazide potentiated AMPA-induced convulsive seizures in a dose dependent manner and caused an extensive loss of CA3/4 pyramidal cells. Pretreatment of 1-NA-Spm inhibits both cyclothiazide potentiated AMPA-induced convulsive seizures and degeneration of pyramidal cells.In amygdaloid kindled animals, 1-NA-Spm dose-dependently improved seizures and shortend the discharge duration 30 min after the administration. The anticonvulsant effect was observed even one day after the frug, and then gradually disappeared within 4 days.The present findings demonstrate that 1-NA-Spm acts as a potent and long-acting anticonvulsant and would be possible candidate for new antiepileptic drug.