The mode of action of several opioids on cardiac muscle

Abstract

SUMMARYThe objective of the experiments was to investigate the cellular basis of the inotropic effect on myocardium of several opioids which have been implicated in producing cardiotoxic effects in human poisioning. Opioids exerted negative inotropic effects, with half-maximal concentrations between 10 /LM (dextropropoxyphene) and 118 /,M (pethidine); all agents reduced the magnitude of the intracellular Ca2+ transient and the L-type Ca2+ current, ICa, over a similar concentration range to that which reduced twitch tension. The depression of ICa correlated positively with the value of the opioid oil-water partition coefficient. Effects were not antagonized by the opioid receptor antagonist naloxone. Action potential upstroke rate was also reduced but at significantly higher concentrations. Resting potential and action potential duration were not consistently affected; none of the opioids tested altered intracellular pH. These data suggest that opioids exert a negative inotropic effect by their action on ICa; blockade of the Na+ current is not great enough to exert a significant action. The lack of effect of naloxone implies the actions are independent of the opioid receptor. The correlation of effects with the oil-water partition coefficient implies a nonspecific effect dependent on the hydrophobicity of the agent.

A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning

“…Furthermore, morphine perfusion significantly reduced contractile force and shortened survival of the perfused heart despite a significant reduction in oxygen consumption. The negative inotropic and chronotropic actions of morphine and other opioids have been reported previously (11,12,29,33), and they are thought to be mediated by ␦-or -opioid receptors (3) or nonopioid receptors (33). Reports of positive inotropic action of morphine in intact animals are thought to be the result of sympathoadrenal discharge (30).…”

Inibição da corrente de cálcio tipo L por tramadol e enantiômeros em miócitos cardíacos de ratos

“…However, its cardioprotective effect is known to be due to the activation of d-receptors 26,27 . Studies have shown that opioids like dextropropoxiphene, pethidine and leucine enkephalin reduce I Ca-L but only the inhibition induced by d-receptor agonist (leucine enkephalin) was blocked by naloxone 28,29 . The effects of tramadol on other ionic currents also suggest a direct effect on L-type Ca 2+ channels.…”

Dextropropoxyphene and the cardiovascular system: About two cases of acute poisoning with cardiac conduction abnormalities

“…13 DP also exerts a negative inotropic effect by its blockage of the inward calcium current. 14 Moreover, DP and NP dilate the systemic and coronary vascular beds. 10 The clinical use of naloxone to reverse DP cardiotoxicity is still being discussed.…”