Stereoselectivity of arrhythmogenic effect of praziquantel in conscious rabbits

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.