Qian Y S, Quan Y Z
Zhongguo Yao Li Xue Bao. 1989 May;10(3):245-8.
Praziquantel (PQT) is a chiral compound with an asymmetric center at the 11 b-position. The recemic mixture is usually used as an antischistosomal drug, however the antischistosomal activity is mainly concentrated in the R (-)-enantiomer. This study was undertaken to investigate the stereoselectivity of the arrhythmogenic effect of PQT in conscious rabbits. Arrhythmias, as well as bradycardia, were induced in rabbits by iv (+/-) PQT or its enantiomers at 45 mg/kg. The frequency of ectopic rhythms in the (+), (+/-) and (-) PQT groups were 100, 60 and 20%, respectively. Statistically, the frequency of ectopic rhythms in the (+) PQT group was significantly higher than those in the (-) PQT group and in the (+/-) PQT group, although there was no significant difference between the (+/-) and (-) PQT groups. The severity of the arrhythmias induced by (+) PQT was much higher than that induced by (-) PQT. The bradycardia action of (+) PQT was much more intense than that of (-) PQT. (+/-) PQT or its enanthiomers (icv) at a dose of 2 or 3 mg/kg also induced arrhythmias. The frequency of ectopic rhythms in the (+) PQT group was significantly higher than that in the (-) PQT group. The results suggest that there is a stereoselectivity of the arrhythmogenic effects of PQT in rabbits. Arrhythmias induced by PQT may partly mediated via the central nervous system, and the arrhythmogenic effects of (+/-) PQT may be caused mainly by (+) PQT.
吡喹酮（PQT）是一种在11β位具有不对称中心的手性化合物。消旋混合物通常用作抗血吸虫药物，然而抗血吸虫活性主要集中在R（-）-对映体中。本研究旨在调查PQT在清醒家兔中致心律失常作用的立体选择性。通过静脉注射45mg/kg的（+/-）PQT或其对映体在兔中诱发心律失常以及心动过缓。（+）、（+/-）和（-）PQT组的异位节律频率分别为100%、60%和20%。统计学上，（+）PQT组的异位节律频率显著高于（-）PQT组和（+/-）PQT组，尽管（+/-）和（-）PQT组之间没有显著差异。（+）PQT诱发的心律失常严重程度远高于（-）PQT诱发的。（+）PQT的心动过缓作用比（-）PQT强烈得多。2或3mg/kg剂量的（+/-）PQT或其对映体（脑室内注射）也诱发心律失常。（+）PQT组的异位节律频率显著高于（-）PQT组。结果表明PQT在兔中致心律失常作用存在立体选择性。PQT诱发的心律失常可能部分通过中枢神经系统介导，且（+/-）PQT的致心律失常作用可能主要由（+）PQT引起。
