Influence of the optical isomers (+)- and (-)-naloxone on beating frequency, contractile force and action potentials of guinea-pig isolated cardiac preparations

Abstract

Naloxone in concentrations ranging from 7.5 to 120 mumol l-1 reduced the beating frequency of guinea-pig isolated atria. The ED50 was 7.9 mumol l-1 for the (-)-isomer and 10.8 mumol l-1 for the (+)-isomer. Concentrations up to 120 mumol l-1 of either (-)- or (+)-naloxone did not affect the force of contraction of left atria stimulated at 1 Hz. In concentrations from 30 to 120 mumol l-1 (-)-naloxone increased the action potential (AP) duration and the functional refractory period (FRP) of papillary muscles. The resting membrane potential and the AP amplitude remained unchanged, while a small decrease of Vmax was seen with the larger drug concentrations. The influence of (+)-naloxone (120 mumol l-1) was comparable to that of the (-)-isomer. The influence of morphine (120 mumol l-1) on papillary muscle AP was small. AP duration and FRP showed a marginal prolongation while Vmax was slightly decreased. (-)-Naloxone 60 mumol l-1 had no effect on slow-response APs of K+-depolarized papillary muscles. Slow-response APs were abolished by verapamil (1 mumol l-1). In left atrial strips the prolongation of the AP duration produced by 120 mumol l-1 of either (-)- or (+)-naloxone resembled the drug effect in papillary muscles. Most of the observed changes can be explained by an inhibition of the time-dependent membrane K+ outward current, an effect of naloxone that may be classified as a Class III antiarrhythmic action. Apparently this effect is not mediated by stereospecific opioid receptors.