Research and development of common model of epilepsy with fumitremorgin-like central nervous stimulative compounds.

烟曲霉素A（FTA）是一种真菌代谢产物，具有强烈的中枢神经兴奋作用。这种作用被一些已知的抗惊厥药和2-氨基-5-膦酰基庚酸（APV）抑制，2-氨基-5-膦酰基庚酸（APV）是谷氨酸受体的激动剂，例如N-甲基-d-天冬氨酸（NMDA）。本研究结果提示FTA可用于实验动物癫痫模型的诱导，为抗癫痫药物的筛选提供依据. FTA相关化合物的合成：以6-甲氧基色氨酸甲醚为起始原料，经Pictet-Spengler反应、与L-脯氨酸缩合、脱氢等反应，合成了一个含吲哚环的五环化合物，以此化合物为关键化合物，合成了36个FTA相关化合物，为研究其致惊厥性和对NMDA受体的影响提供了样品.癫痫惊厥效力的测定：在加入和不加入FTA相关化合物的情况下，测定^3 H-谷氨酸、^3 H-天冬氨酸和^3 H-APVc与小鼠脑P-2组分的结合效力。结果表明，FTA是一种可能的先导化合物，可用于研究和开发制备癫痫模型的有效致痫剂。

Fumitremorgin A(FTA), a fungal metabolite having a potent central nervous stimulative effect, was found to cause the abnormal behayiors resembling to the eliptic convulsion to mice. The effect was suppressed with some known ant-convulsants and 2-amino-5-phosphonoheptanoic acid(APV), an agonist of the stimulants for glutamate receptor for instance for N-methyl-d-aspartate(NMDA). The finding suggested a possibility that FTA is to be used for the induction of the epilepsy model to the experimental animals, which are useful for the screening of anticonvulstants or antiepileptic reagents.1. Syntheses of FTA-related compounds : From 6-methoxytryptophan methylether, a five cyclic compound containing indole ring was synthesized through Pictet-Spengler reaction, condensation with L-proline, dehydrogenation etc. By using this compound as a key compound, 36 FTA-related compounds were synthesized and provided as samples for the examination of the convulsive property.and the effect on the NMDA receptor.2. Measurement of the epileptic convulsive potency : The binding potency of ^3H-glutamate, ^3H-aspartate and^3H-APVc to the P-2fraction from mouse brain was measured with and without the FTA-related coumpounds. The exhibition of abnormal behaviors in mice with and without those samples was also observed.FTA was found conclusively to be a possible lead compound for research and development of the useful convulsant to make the epilepsy model.