3种5-HT_4受体激动剂对胃肠道动力与心功能影响的实验研究

Effects of Three 5-HT_4 Receptor Agonists on Gastrointestinal Motility and Cardiac Function

目的检测3种5-羟色胺4(5-HT_4)受体激动剂对胃肠道动力与心功能的影响,以期找到既具胃肠动力又无心脏副作用的药物。方法分别应用炭末法和张力换能器以及Langendorff离体灌流装置,观察西沙必利、RS67506和扎考必利低剂量、中等剂量、高剂量3种剂量对小鼠和大鼠胃肠动力与心功能影响。结果扎考必利和RS67506在剂量稍大的条件下,具有与西沙必利相同的促肠道动力作用;西沙必利在1μmol/L^30μmol/L范围内对大鼠心律影响较大,出现室性期前收缩和二联律,对心功能无显著变化。RS67506和扎考必利在一定的浓度范围内对大鼠心脏无致心律失常作用,对心功能也无影响。结论西沙必利、RS67506和扎考必利均可不同程度地促进小鼠肠推进运动并增加大鼠离体肠管环行肌的收缩张力;西沙必利在具有致心律失常作用,而RS67506和扎考必利则无此副作用。

Objective To investigate the effects of three5HT4receptor agonists on gastrointestinal motility and cardiac function inorder to find a drug that has both gastrointestinal motility and no cardiac adverse effects.Methods Using charcoal method,tensiontransducer and Langendorff perfusion respectively,we researched the effects of Cisapride,RS67506and Zacopride on gastrointesti-nal motility,cardiac function and ECG in low dose,moderate dose and high dose of three doses in mice and rats.Results At thehigher dosage,Zacopride and RS67506has the same prokinetic effects as Cisapride,Cisapride(1μmol/L^30μmol/L)induced ar-rhythmia,and the main pattern was ventricular premature contraction and coupled rhythm,left ventricle functions was decreased andthe heart rate was slow down.RS67506and Zacopride had no arrhythmic effect on heart of rats in a certain concentration range,andhad no effect on cardiac function.Conclusion Cisapride,RS67506and Zacopride could promote the intestinal propulsion in mice andincreased intestinal smooth muscle contraction in rat;Cisapride has the arrhythmogenic effect in this experiment,RS67506andZacopride had no side effect.Therefore,we draw a conclusion that RS67506and Zacopride are two more safe alternative drugs forthe treatment of functional disorders of the gastrointestinal tract than Cisapride.