氟哌啶醇季铵盐衍生物对冠状动脉作用的研究

 目的：研究氟哌啶醇季铵盐衍生物(F₂)对动物冠状动脉的作用。方法：小鼠ip氟哌啶醇(10mg·kg^-1和20mg·kg^-1)造成锥体外系不良反应模型。Ip F₂(10mg·kg^-1,20mg·kg^-1和40mg·kg^-1)，观察行为变化?采用猪冠脉条生物检定，观察10^-6mol·L^-1，10^-5mol·L^-1和10^-4mol·L^-1F₂对KCl(10mmol·L^-1～40mmol·L^-1)致猪冠脉条收缩量效曲线的影响，并观察10^-4mol·L^-1F₂对KCl(20mmol·L^-1)致冠脉条收缩后的阻断作用?采用Langendorf灌流法，观察10^-6mol·L^-1，5×10^-6mol·L^-1和10^-5mol·L^-1F₂对脑垂体后叶素所致离体豚鼠心脏冠脉流量减少的作用。结果：氟哌啶醇可致小鼠肌张力增高，肌震颤、头颈部扭曲和尾过伸等，有量效依赖性。F₂3个浓度组无一出现上述表现。F₂可使KCI致猪冠脉条收缩曲线压低，呈量效依赖性。F₂量效依赖地拮抗脑垂体后叶素致冠脉流量的减少。结论：ipF₂不引起锥体外系不良反应，但有扩冠作用。

The effect of quaternary ammonium salt derivation of haloperidol on coronary artery

OBJECTIVE: To observe the effect of quaternary ammonium salt derivation of haloperidol on coronary artery. METHODS: The model of adverse reaction of extrapyramidal system induced by haloperidol ip on mice was used to observe the behavior effect of its derivation (F₂). Using the bioassay of porcine coronary artery strips, we added F₂ (10^-6，10^-5 and 10^-4) into the bath medium prior to KCl (10～40 mmol·L^-1) administration respectively to observe the effect of F₂ on dose response curve of contraction induced by KCl, and the block action of F₂(10mg·kg^-4,20mg·kg^-1 on the contraction induced by KCl; using the Langendorff perfusion, we also observed the effect of F₂ (10^-6, 5×10^-6, 10^-5 mol·L^-1) on reduction of coronary artery blood flow of guinea-pig induced by pituitrin. RESULTS: Haloperidol (10 mg·kg^-1 and 20 mg·kg^-1) induced Parkinson's like syndrome, but F₂ (10 mg·kg^-1, 20 mg·kg^-1and 40 mg·kg^-1) can not induce same effects. F₂ lowered coronary artery strips contraction curve induced by KCl in dose-dependent manner. F₂ also blocked the contraction by KCl. F₂ antagonized the reduction of coronary flow induced by pituitrin on isolated heart of guinea-pig in dose-dependent manner. CONCLUSION: F₂ caused coronary artery dilation as haloperidol, and could not cause any adverse reaction of extrapyramidal system.