欢迎访问《中国临床药理学与治疗学》杂志官方网站,今天是

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (9): 966-969.

• 研究原著 • 上一篇    下一篇

盐酸戊乙奎醚外消旋体及其4 个光学异构体在小鼠脑中的测定及[3H]-二苯基羟乙酸奎宁酯对其分布的影响

薛明1,2, 张振清2, 袁淑兰2, 乔建忠2, 刘克良2, 阮金秀2   

  1. 1首都医科大学药理学系, 北京100054;
    2军事医学科学院毒物药物研究所, 北京100850
  • 收稿日期:2004-02-12 修回日期:2004-08-21 出版日期:2004-09-26 发布日期:2020-11-23
  • 通讯作者: 薛明, 男, 博士后, 研究员(教授), 研究生导师, 研究方向: 药物代谢及新药研究。Tel:010-63051453 E-mail:xuemd @163. net
  • 基金资助:
    国家自然科学基金重大项目资助课题(№203900508)

Distribution of penehyclidine hydrochloride raceme and effects of QNB on its four optical isomers in mice brain

XUE Ming1,2, ZHANG Zhen-Qin2, YUAN Shu-Lan2, QIAO Jian-Zhong2, LIU Ke-Liang2, RUAN Jin-Xiu2   

  1. 1Department of Pharmacology, Capital University ofMedical Sciences, Beijing 100054, China;
    2Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
  • Received:2004-02-12 Revised:2004-08-21 Online:2004-09-26 Published:2020-11-23

摘要: 目的: 研究盐酸戊乙奎醚外消旋体及其4 个光学异构体在小鼠脑中的分布及QNB 对其分布的影响。方法: 应用GC-MS SIM 定量方法测定了盐酸戊乙奎醚外消旋体与其4 个光学异构体在小鼠脑中药物浓度。结果: 盐酸戊乙奎醚外消旋体及其4 个异构体在小鼠脑中均存在较高的分布浓度, 各异构体在脑中的分布特点是, 与M 受体亲和力较大的R-2 异构体在脑中具有较高的选择性分布浓度。R 型异构体在脑中消除慢, 而S 型异构体在脑中消除快。给予一定剂量的QNB, 可明显降低各异构体在小鼠脑中的分布水平, 其中药效作用较大的R-2 异构体受QNB 的影响更大。说明R-2 异构体在脑中占据的M 受体位点多, R-2 异构体的分布主要与M受体的立体特异性结合有关。结论: 盐酸戊乙奎醚异构体在小鼠脑中的分布与mAChR 的亲和力存在相关性,QNB 对盐酸戊乙奎醚外消旋体及其4 个异构体在小鼠脑中的分布有显著影响。

关键词: 盐酸戊乙奎醚, 光学异构体, QNB, 分布, 影响, GC-MS SIM

Abstract: AIM: To study the distribution of penehyclidine hydrochloride (PHC) raceme and its four optical isomers in mice and the effects of QNB on distribution of PHC.METHODS: The tissue concentrations of PHC raceme and its four optical isomers in mice were determined by gas chromatography-mass spectrometry with selected ion monitoring (GC-MS/SIM) PHC (m/z 175) and PHC-5 (m/z 180) as internal standard.RESULTS: The main pharmacokinetic parameters of PHC raceme in mice brain after im a single dose (0.1 mg·kg-1) were as follows: T1/2β = 35.16±5.4 h, Cmax = 66.98±12.6 ng·g-1, and AUC = 2.1±0.4 μg·h-1·g-1. The distribution concentrations in brain had a significantly persistent level for more than 48 h. PHC raceme and the four optical isomers were high selectively distributed in mice brain. The results showed that the concentration of distribution of R-2 isomer had a higher level. And the isomer with S-configuration in mice brain eliminated fast and isomer with R-configuration eliminated slowly. And the tissue concentration of R-2 isomer had a high level which R-2 isomer had a great affinity with mAChR.The distribution concentration of the four optical isomers in mice brain obviously decreased after or before QNB was given. Among them, the R-2 isomer was influenced more greatly by QNB, which R-2 had the highest biological potency. It suggested that the distribution of R-2 isomer in mice brain was mainly related to mAChR.CONCLUSION: There is a relationship between the tissue concentration of the isomer in mice brain and the affinity of the isomer to mAChR. QNB can affect the distribution of PHC and its four isomers in mice brain.

Key words: penhyclidine hydrochloride, optical isomers, QNB, distribution, GC-MS/SIM

中图分类号: