EFFECTS OF PRAZIQUANTEL AND ITS ENANTIOMERS ON THE PHYSIOLOGICAL PROPERTIES OF ISOLATED RAT ATRIA

The stereoselectivity of the arrythmic effect of praziquantel (PQT)which contained a chiral carbon at position 11b of its moiety was reported in the previous study. In this study the effects of enantiomers of PQT on the physiological properties of isolated rat atria were shown to be different. ED₅₀ of (±)-,(+)-and (-)-PQT calculated from the log dose-positive inotropic effect curve in left atria were 14.8, 16.6 and 48.0 μmol/L, respectively. The Emax of (-)-PQT was 49± 11% increase in contractile force, whereas that of (+)- and (±)- PQT were 85± (SD)15% and 79±(SD)4%, respectively. Verapamil in a very low concentration of 0.1μmol/L or 0.5 μmol/L antagonized the positive inotropic effects of PQT and its enantiomers very markedly. In low concentration(30μmol/L) only (+)-PQT and (±) PQT exhibited bradycardiac effect while in higher concentration (100 μmol/L) all three drugs exerted the same effect. These drugs could also induce arrythmias in right atria, but the frequency of arrythmias occurred in the right atria treated with (+)-PQT was much higher than that treated with (-)-PQT. (+)-PQT shortened the refractory period and decreased the automaticity of the left atria but (-)-PQT did not exert any effect on the refractory period and automaticity.