2′,4′-二氯苯基哒嗪衍生物的抗小鼠癫痫作用

本文对2′,4′-二氯苯基哒嗪衍生物对几种实验性癫痫模型的对抗作用进行了研究,其中化合物Ⅰ和Ⅱ对最大电休克发作实验(MEST),戊四唑(Met)印防己毒素发作和荷包牡丹碱发作等四种实验性癫痫模型均有很强的对抗作用,强于苯妥英钠,苯巴比妥和卡马西平,但也显示中枢抑制作用,预防指数不高,化合物Ⅲ和Ⅳ对这四种动物惊厥模型亦有较强的对抗作用,均大大强于丙戊酸钠和乙琥胺,其中化合物Ⅲ的中枢神经系统毒性较低,抗MEST的预防指数高达23.4.

Antiepileptic action of 2', 4'-dichlorophenylpyridazinederivatives in mice

2′ 4′-Dichlorophenyl pyridazine, a new type of anticonvulsant, could protect mice from seizures test produced by maximal electroshock, metrazol (Met), picrotoxin and bicuculline. CompoundⅠandⅡantagonized the four experimental seizures with an overall potency superior to that of phenytoin, phenobarbital and carbamazepine. Compound Ⅲ and Ⅳ protected mice from chemically induced seizures and the efficacy of them was superior to that of valproate and ethosuximide. Compound Ⅲ antagonized maximal electroshock seizure test (MEST) and was as potent as phenobarbital. It showed a low neurotoxicity on the central nervous system and its pro-tective index (PI) was 23.4 in protecting mice from MEST. Based on these results it was postulated that these compounds were a potent broad spectrum anticonvulsant and may be of benefit to the treatment of epileptic disorders.