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。
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: T 1/2β= 35.16± 5.4 h, C max= 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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2004年第9期966-969,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金重大项目资助课题 (№ 2 0 3 90 0 5 0 8)
