中文摘要：

目的：研究Ⅲ类抗心律失常药对氯苄基四氢小檗碱（CPU-86017）及其12个手性衍生物，分别观察其对麻醉小鼠血压及大鼠血管活性的作用。方法：zh-005～zh-008为对硝基苄基四氢小檗碱溴化物的4个立体异构体，zh-009～zh-012为N-苄基四氢小檗碱氯化物的4个立体异构体。通过对麻醉小鼠i．v．3mg／kgCPU-86017或zh-005～zh-012并连续观察3h，研究其对小鼠血压的影响；通过对大鼠离体主动脉梯度给予CPU-86017或zh-009～zh-012，研究其对去氧肾上腺素（Phe）或KCI引发的血管收缩活性的影响。结果：CPU-86017在改变对氯苄基为对硝基苄基或N-苄基后，只有zh-006对血压的影响最小，提示其i．v．毒性亦最小。CPU-86017的4个立体异构体，对a1A效应（ROC）呈现立体选择性抑制，而对电压依赖钙通道（VOC）抑制的立体选择性不明显。结论：对氯苄基四氢小檗碱类化合物与血管α1A受体的结合能力，可能取决于结构式中C-13a的构型。

英文摘要：

AIM： To compare the effects of III Class antiarrhythmie CPU-86017 （p-ehlorobenzyl-tetrahydroberberine） and its 12 optical derivates on mouse blood pressure and rat aortic contractile activity. METHODS： Zh- 005 to zh-008 are 4 stereoisomers of p-nitrobenzyl-tetra- hydroberberine, and zh-009 to zh-012 are 4 stereoisomers of N-benzyl-tetrohydroberberine. In this study, CPU- 86017 or zh-005 - zh-012 at dose of 3 mg/kg were i.v. in anaesthetized mice, and the blood pressure was monitored by arterial cannulation for 3 hours. CPU86017 or zh-001 to zh-004 （the 4 stereoisomers of CPU-86017） was administered in gradient dosage to rat aorta in vitro for evaluation the effects on aortic contraction induced by Phe and KCl. RESULTS： The least potency on blood pres-sure of CPU-86017 and zh-005 - zh-012 was found by iv zh-006, which suggested the least side effect. By study of the inhibitory effects on rat aortic contraction of CPU86017 and zh-001 to zh-004, we found that the stereoisomers showed a stereoselectivity on suppressing the receptor related Ca^2＋ channel （ROC）, but not the voltage dependent Ca^2 ＋ channel （VOC）. CONCLUSION： The configuration of C-13a in the structural formula of p-chlorobenzyl- tetrahydroberberine might be dominant to its affinity to α1A receptor.