氟哌啶醇季铵盐衍生物的生物活性研究

Effects of uaternary ammonium salt derivatives of haloperidol on hemodynamics in rats

目的：探讨氟哌啶醇季铵盐衍生物F8～F13的离体扩冠活性及对麻醉大鼠整体血流动力学的影响，并分析构效关系。方法：采用生物检定法，观察20μmol／L目的化合物对KCl诱导的猪冠脉螺旋条收缩曲线的影响；麻醉正常血压SD大鼠，经右颈总动脉插管至左心室，右股动脉插管后，分别5mg／kg静脉注射6个目的化合物，BL-420型生物机能实验系统记录观察血流动力学效应。结果：F11和F13均具强的降压作用：其中F13兼具良好的扩冠活性，同时在其降低血压的同时可能对SD大鼠具心功能抑制作用，而F11对大鼠心功能无影响。结论：苄基苯环上以对位或邻位甲基取代者更适合作为进一步研究与开发心血管药物的理想先导物。

Objective： To study the effects of quaternary ammonium salt derivatives of haloperidol F8-F13 on hemodynamics in rats and to find out the relationship between the structure and activity. Methods： To observe the effects of the compounds （20μmol/L） on dose-response curve of contraction induced by KCl in isolated porcine coronary artery spiral strips by using the bioassay. The catheters were inserted into the right femoral artery and the left ventricle through right common carotid artery. After i. v. administration of 6 kinds of compounds at the dose of 5 mg/kg in anaesthetized rats, the hemodynamic indexes were analyzed by BL-420 biological function experiment system. Results., Both Fll and F13 significantly decreased blood pressure . F13 could enlarge coronary artery and inhibit the cardiac functions of the rats at the same time, while Fll had no effect on heart functions of the rats. Conclusion： Quaternary ammonium salt derivatives of haloperidol substituted by methyl （o- or p-） should be the appropriate lead-compound as the cardiovascular drugs.