Depression of myocardial contractile function by propoxyphene and norpropoxyphene

Ezra A Amsterdam, S. V. Rendig, G. L. Henderson, D. T. Mason

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Propoxyphene and its principal metabolite, norpropoxyphene, depressed maximum developed isometric tension (T) and its first derivative, dT/dt, in isolated cat right ventricular papillary muscles. T and dT/dt were reduced by 10-5 M concentrations of each drug (p<0.005), and this effect was markedly intensified at 10-4 M: propoxyphene, 49% reduction of T (p<0.001); norpropoxyphene, 36% reduction of T (p<0.001). Nonresponsiveness to electrical stimulation developed in the majority of muscles at the 10-5 M concentration of each drug and in all muscles at 10-4 M. The cardiac depressant actions of the two drugs administered simultaneously at a concentration of 10-5 M each were additive, resulting in a 15.6% decline in T. The contractile actions of propoxyphene and norpropoxyphene were not altered by the specific narcotic blocking agent, naloxone, indicating these effects were produced by a nonopiate mechanism. In contrast to propoxyphene and norpropoxyphene, morphine produced no reductions in T or dT/dt at a concentration of 10-5 M and only a slight, albeit significant (p<0.05), depression of T (-4%) and dT/dt (-6%) at 10-4 M. The cardiac depressant effects of propoxyphene and norpropoxyphene were at least partially reversible, as indicated by substantial recovery of contractile function after drug removal (to 69-75% of control T) and by a positive inotropic response to isoproterenol. These results indicate that at high concentrations propoxyphene and norpropoxyphene have a cardiac depressant action characterized by decreased electrical excitability and reversible contractile depression, effects which are consistent with a local anesthetic action. Depression of cardiac contractile and electrophysiologic functions by propoxyphene and norpropoxyphene may play a role in the clinical toxicity associated with propoxyphene overdose.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume3
Issue number1
StatePublished - 1981

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Dextropropoxyphene
Anti-Arrhythmia Agents
Pharmaceutical Preparations
Muscles
Papillary Muscles
norpropoxyphene
Narcotics
Recovery of Function
Naloxone
Local Anesthetics
Isoproterenol
Morphine
Electric Stimulation
Cats

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Depression of myocardial contractile function by propoxyphene and norpropoxyphene. / Amsterdam, Ezra A; Rendig, S. V.; Henderson, G. L.; Mason, D. T.

In: Journal of Cardiovascular Pharmacology, Vol. 3, No. 1, 1981, p. 129-138.

Research output: Contribution to journalArticle

Amsterdam, Ezra A ; Rendig, S. V. ; Henderson, G. L. ; Mason, D. T. / Depression of myocardial contractile function by propoxyphene and norpropoxyphene. In: Journal of Cardiovascular Pharmacology. 1981 ; Vol. 3, No. 1. pp. 129-138.
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abstract = "Propoxyphene and its principal metabolite, norpropoxyphene, depressed maximum developed isometric tension (T) and its first derivative, dT/dt, in isolated cat right ventricular papillary muscles. T and dT/dt were reduced by 10-5 M concentrations of each drug (p<0.005), and this effect was markedly intensified at 10-4 M: propoxyphene, 49{\%} reduction of T (p<0.001); norpropoxyphene, 36{\%} reduction of T (p<0.001). Nonresponsiveness to electrical stimulation developed in the majority of muscles at the 10-5 M concentration of each drug and in all muscles at 10-4 M. The cardiac depressant actions of the two drugs administered simultaneously at a concentration of 10-5 M each were additive, resulting in a 15.6{\%} decline in T. The contractile actions of propoxyphene and norpropoxyphene were not altered by the specific narcotic blocking agent, naloxone, indicating these effects were produced by a nonopiate mechanism. In contrast to propoxyphene and norpropoxyphene, morphine produced no reductions in T or dT/dt at a concentration of 10-5 M and only a slight, albeit significant (p<0.05), depression of T (-4{\%}) and dT/dt (-6{\%}) at 10-4 M. The cardiac depressant effects of propoxyphene and norpropoxyphene were at least partially reversible, as indicated by substantial recovery of contractile function after drug removal (to 69-75{\%} of control T) and by a positive inotropic response to isoproterenol. These results indicate that at high concentrations propoxyphene and norpropoxyphene have a cardiac depressant action characterized by decreased electrical excitability and reversible contractile depression, effects which are consistent with a local anesthetic action. Depression of cardiac contractile and electrophysiologic functions by propoxyphene and norpropoxyphene may play a role in the clinical toxicity associated with propoxyphene overdose.",
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