Depression of Myocardial Contractile Function by Propoxyphene and Norpropoxyphene

Abstract

Summary: 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 ³ M concentrations of each drug (p < 0.005). and this effect was markedly intensified at 10 ¹ 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 ³ M concentration of each drug and in all muscles at 10 ³ M. The cardiac depressant actions of the two drugs administered simultaneously at a concentration of 10 ³ 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.