顺-3,4-二氯-α-氯代桂皮酰另丁胺的抗实验性癫痫作用及其机制的研究

顺—3,4—二氯—α—氯代桂皮酰另丁胺(代号:8601)为一种新的桂皮酰胺类化合物。它对MES有很强的对抗作用,其EK_(50)为20.3mg/kg,明显强于抗痫灵(ED_(50)为88.5mg/kg)。前者的治疗指数>44.3,后者为6.3。所以,8601有可能成为一种作用强、安全范围大的新的抗癫痫药。它也能有效的对抗icv谷氨酸钠和ZnSO_4所引起的惊厥,但对士的宁惊厥则无明显影响。8601抗最大抗电休克发作试验作用的机制可能与其升高脑中5HT和降低中枢兴奋性神经递质Glu和AsP的含量有关。

STUDIES ON THE ANTAGONISM OF 8601 AGAINST EXPERI-MENTAL EPILEPSY IN MICE

Cis-3, 4-dichloro -a-chloro-cinnamoyl-sec.-butylamine (8601), a new compound of cinnamamides, has potent antagonistic effect on experimental epilepsy. 8601 is significantly more effective against MES in mice than Antiepilepsirine. It has also been found effective against convulsion induced by icv. injection of sodium glu-tamate and zinc sulfate. The mechanisms of anti-MES of 8601 is related to content of 5 HT in the whole brain of mice. Increased cerebral 5 HT with L-tyrosine potentiated the effect of anti-MES of 8601,while the opposite was obtained using reserpine or pCPA which decreased the concentration of cerebral 5 HT. The increase of cerebral 5 HT is correlated with the effect of anti-MES of 8601 with a correlation coefficient of 0.926 ( P<0 .025 ). Apart from this,8601 can also decrease the content of aspartic acid and glutamic acid in the whole brain of mice; therefore, may also help in anticonvulsion of 8601.