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

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

  • 1990-01-01
Published in:
  • Journal of cardiovascular pharmacology. - 1990
Animals
Arrhythmias, Cardiac
Biotransformation
Chromatography, High Pressure Liquid
Male
Myocardial Reperfusion Injury
Propafenone
Rats
Rats, Inbred Strains
Stereoisomerism
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/131354
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