The Relative Potency of Major Metabolites and Enantiomers of Propafenone in an Experimental Reperfusion Arrhythmia Model

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Abstract
We used isolated rat hearts subjected to coronary artery ligation and reperfusion to study the antiarhythmic activity of 5-hydroxypropafenone (5OHP) and β-depropylpropafenone (NDPP), major metabolites of Iropafenone (P) in humans, and of the two enantiomers R)- and (S)-propafenone. 5OHP suppressed reperfusion rhythmias similar to the parent drug in a concentration ependent manner. The concentration of 5OHP needed to revent ventricular fibrillation in 50% of experiments EC50) was significantly higher than that of P (0.186 ± 0.05 vs. 0.153 ± 0.005 mg/L, mean ± SEM, p < 0.05). SOHP had a relative potency of 80% compared to P. When 5OHP and P were administered together, their antiarrhythmic effect appeared to be supra-additive. The NDPP metabolite showed very little antiarrhythmic potency and was about four times less active than P. The two enantiomers (R) and (S) were equipotent and showed antiarrhythmic activities similar to racemic P.