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已知二苯基丙基乙酸β-二乙基氨基乙酯(SKF 525A)为肝微粒体药物轉化酶的抑制剂。我們以戊巴此妥鈉睡眠时間为指标,发現SKF 525A的作用是双相的。小鼠注射一剂SKF 525A(40—80毫克/公斤)后0—12小时为莉酶受抑制期,表現为戊巴比妥鈉睡眠时間明显延长;但注射后48小时,小鼠戊巴比妥鈉睡眠时間不仅不延长,反而縮短。SKF 525A的双相效应在雌雄小鼠均能看到。小鼠及大鼠經連續多次注射SKF 525A后48小时,同样也出現第二相效应。下述进一步的实驗表明第二相效应是由于肝脏药物轉化酶活性加強的結果:(1)48小时前接受过一剂SKF 525A的小鼠,戊巴比妥鈉自体內消失的速率此正常动物者明显加快。(2)不論48小时前是否接受过SKF 525A,小鼠戊巴比妥鈉睡眠刚醒时,体內催眠药含量无显著差別。(3)48小时前曾經注射SKF 525A的大鼠肝切片轉化戊巴比妥鈉的速率比正常动物肝切片者快。(4)48小时前注射SKF525A并不改变二乙基巴比妥鈉(一个在体內不經轉化的莉物)引起的小鼠睡眠时間及其自体內消失的速度。 給小鼠(或大鼠)注射相当剂量的SKF 525A后12—24小时,肝脏(及尿)中的維生素C含量比对照动物者显著增加。但在給药后48小时,此作用即已消失。可見SKF525A对动物体內維生素C合成的促进作用出現在对肝脏莉物轉化酶的刺激作用之前。
Beta-diethylaminoethyl diphenylpropyl acetate (SKF 525A) is known as an inhibitor of hepatic microsomal drug-converting enzyme. We pentobarbital sodium sleep time as an indicator, found that the role of SKF 525A biphasic. Mice injected with a dose of SKF 525A (40-80 mg / kg) 0-12 hours for the inhibition of li enzyme, the performance of pentobarbital sodium significantly prolonged sleep; but 48 hours after injection, mice pentobarbital Than sodium sodium sleep time not only prolonged, but shortened. The biphasic effect of SKF 525A can be seen in both male and female mice. A second phase effect also occurred 48 hours after repeated injections of SKF 525A in mice and rats. The following further experiments showed that the second phase effect was the result of an increase in hepatic drug-converting enzyme activity: (1) mice that received a single dose of SKF 525A 48 hours prior to the rate at which pentobarbital disappeared from the body in vivo Obviously faster. (2) There was no significant difference in the content of hypnotic drugs in vivo when mice received pentobarbital sodium just after 48 hours had received SKF 525A. (3) The rat liver slices injected with SKF 525A 48 hours earlier were more likely to convert to pentobarbital than the normal animal liver sections. (4) Injection of SKF525A 48 hours earlier did not change the sleep time of mice and the rate of their disappearance in mice caused by diethylbarine sodium (an in vivo non-transformed material). At 12-24 hours after injecting a comparable dose of SKF 525A into mice (or rats), the vitamin C content in the liver (and urine) was significantly increased over the control animals. But at 48 hours after administration, this effect disappeared. It can be seen that the promoting effect of SKF525A on the synthesis of vitamin C in animals appeared before stimulating hepatic invertase.