抗胆碱药盐酸戊乙奎醚减慢健康受试者心率的初步观察

Pilot investigation of anticholinergics penehyclidine hydrochloride:retarding heart rate in healthy subjects

目的：观察盐酸戊乙奎醚对健康受试者心率的影响,初步探讨其作用机制。方法：筛选健康受试者48例,18-40岁,分别入组单次口服和多次给药组。心电图检测7组32例健康受试者单次口服、2组16例健康受试者多次口服盐酸戊乙奎醚片前后心率变化。结果：单次和多次给药受试者给药后心率显著减慢（P﹤0.05）。32例单次给药和16例多次给药受试者多数在试验中出现窦性心动过缓和窦性心律不齐。单次给药受试者给药前正常、给药后异常心电图23例,1例受试者发生Ⅰ度房室传导阻滞、频发房性早搏等不良事件。多次给药受试者给药前正常、给药后异常10例,1例受试者发生Ⅰ度房室传导阻滞。结论：盐酸戊乙奎醚可能通过非M2受体途径介导心脏传出神经调节心脏功能,进而减慢心率,这一效应及其临床意义尚待深入研究。

AIM： To observe the effect of penehyclidine hydrochloride on heart rate,explore the pharmacological mechanism combining with its clinical applications.METHODS： Healthy subjects（18-40 years old） were enrolled in a randomized,opened,parallel study.The subjects were randomized to orally receive either penehyclidine hydrochloride 0.1-1.0 mg daily（n=32,7 groups） or 0.6,0.8 mg daily（n=16,2 groups） for 1 week.Electrocardiography was used to investigate the changes in heart rate and other abnormity.RESULTS： Statistical significance in the changes of heart rate was observed in the single- and multiple-dose groups（P〈0.05）.Sinus bradycardia and sinus irregularity were observed in the majority of subjects in two groups.First degree atrioventricular block and frequent atrial premature beats were caught sight of in individual subjects in single-dose medication group.There was a case of first degree atrioventricular block in multiple-dose medication group.CONCLUSION： Penehyclidine hydrochloride may retard heart rate in healthy subjects through non-M2 receptor channel/by regulating erethism of vagus nerve,which needs to be studied further.