摘要
用掺食法递增安定剂量56 d致小白鼠身体依赖性,肝微粒体蛋白及细胞色素P_(450)含量均显著增加,高于进食安定7 d组,分别为313.0±s 30.56及261.17±s 23.04 mg·g^(-1)肝,P<0.05及3.96±s 0.07和2.60±s 0.52 nmol·mg^1蛋白,P<0.01。戒断后血浆安定浓度随戒断时间延长逐渐降低,而去甲基安定浓度急剧下降,于戒断后24 h达最低水平,以后逐渐回升。而进食安定7 d组的安定及去甲基安定浓度均逐渐下降,二者间无显著性差异。
Diazepam-was administrated to mice for 56 days and 7 days as a mixture of drug in laboratory chow, leading to diazepam physical dependence of mice. The level of hepatic microsomal protein and cytochrome - P_ (450) was measured. The concentration of di- azepam and desmethyldiazepam was determined during the withdrawal phases as well. The results showed that the hepatic microsomal enzymes were induced by diazepam and the degree of induction was related to the dosage and duration of diazepam treatment. The protein and P_(450) contents of hepatic microsome were significantly increased (313. 0 ± s 30. 56 mg . g^(-1) liver and 3.96±s 0.07 nmol . mg^(-1) protein respectively) in the 56 - day group as compared with those in 7-day group (261. 17 ±s 23. 04 mg . g^(-1) liver and 2. 60 ± s 0. 52 nmol . mg^(-1) protein respectively) of diazepam treatment. The value of desmethyldiazepam concentration decreased immediately and significantly after the withdrawal. The lowest concentration appeared in 24 hours after withdrawal which was different from that of di- azepam.
基金
国家自然科学基金
