氟哌啶醇化学衍生物对冠状动脉作用的研究

Effect of haloperidol chemical derivative on coronary artery

目的和方法：用腹腔注射氟哌啶醇（２５ｍｇ／ｋｇ）复制小鼠锥体外系行为不良反应，经相同途径与剂量注入氟哌啶醇季铵盐衍生物（Ｆ３），观察其行为变化。采用猪冠脉条生物检定，观察１０－６ｍｏｌ／Ｌ、１０－５ｍｏｌ／Ｌ和１０－４ｍｏｌ／ＬＦ３对ＫＣｌ（１０～４０ｍｍｏｌ／Ｌ）性猪冠脉条收缩量效曲线的影响，并采用Ｌａｎｇｅｎｄｏｒｆ灌流法，观察１０－６ｍｏｌ／Ｌ、５×１０－６ｍｏｌ／Ｌ和１０－５ｍｏｌ／ＬＦ３对脑垂体后叶素所致离体豚鼠心脏冠脉流量减少的影响。结果：氟哌啶醇可致小鼠头颈部扭曲，动作不协调，尾过伸，震颤等，而Ｆ３无上述作用。Ｆ３可使ＫＣｌ致猪冠脉条收缩曲线压低，并呈量效依赖性。Ｆ３可以量效依赖地拮抗脑垂体后叶素所致冠脉流量的减少。结论：说明Ｆ３无氟哌啶醇样锥体外系不良反应。

Abstract AIM and METHODS:Using the model of adverse reaction of extrapyramidal system induced by haloperidol(25mg·kg -1 ) upon mice,to observe the behavior of its derivative(F 3)with same dose and administration;Using bioassay of porcine coronary artery strips,F 3(10 -6 ,10 -5 and 10 -4 mol·L -1 respectively)were added into the bath medium prior to KCl 10～40 mmol·L -1 administration to observe the effect of F 3 on dose-response curve of contraction induced by KCl; Using Langendorff perfusion, to observe the effect of F 3 (10 -6 ,5×10 -6 ,10 -5 mol·L -1 ) on reduction of coronary artery flow of guinea-pig induced by pituitrin.RESULTS:Haloperidol induced Parkinson's like syndrome,such as,head-neck twisted and ataxy,tail-prolonged and tremors,but F 3 did not induce the same effect. F 3 lowed contraction curve of coronary artery strips induced by KCl in dose-dependent manner.F 3 antagonized the reduction of coronary flow induced by pituitrin on isolated heart of guinea-pig in dose-dependent manner.CONCLUSION:F 3 caused coronary artery dilation as haloperidol,but did not cause any adverse reaction of extrapyramidal system. MeSH Extrapyramidal tracts;Coronary vessels;Haloperidol