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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The relative potency of major metabolites and enantiomers of propafenone in an experimental reperfusion arrhythmia model.

We used isolated rat hearts subjected to coronary artery ligation and reperfusion to study the antiarrhythmic activity of 5-hydroxypropafenone (5OHP) and N-depropylpropafenone (NDPP), major metabolites of propafenone (P) in humans, and of the two enantiomers (R)- and (S)-propafenone. 5OHP suppressed reperfusion arrhythmias similar to the parent drug in a concentration-dependent manner. The concentration of 5OHP needed to prevent 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 less than 0.05). 5OHP 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.[1]

References

  1. The relative potency of major metabolites and enantiomers of propafenone in an experimental reperfusion arrhythmia model. Oti-Amoako, K., Vozeh, S., Ha, H.R., Follath, F. J. Cardiovasc. Pharmacol. (1990) [Pubmed]
 
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