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

• Published in: British journal of pharmacology 1986-08, Vol.88 (4), p.733-740
• Main Author: Brasch, Helmut
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Antiarythmic agents; Biological and medical sciences; Cardiovascular system; Depression, Chemical; Electric Stimulation; Guinea Pigs; Heart Atria - drug effects; Heart Rate - drug effects; Isomerism; Male; Medical sciences; Membrane Potentials - drug effects; Morphine - pharmacology; Myocardial Contraction - drug effects; Naloxone - pharmacology; Pharmacology. Drug treatments; Potassium - metabolism; Verapamil - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1986.tb16245.x

1 Naloxone in concentrations ranging from 7.5 to 120 μmol l−1 reduced the beating frequency of guinea‐pig isolated atria. The ED50 was 7.9 μmol l−1 for the (−)−isomer and 10.8 μmol l−1 for the (+)‐isomer. 2 Concentrations up to 120 μmol l−1 of either (−)− or (+)‐naloxone did not affect the force of contraction of left atria stimulated at 1 Hz. 3 In concentrations from 30 to 120 μmol 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 V̇max was seen with the larger drug concentrations. The influence of (+)‐naloxone (120 μmol l−1) was comparable to that of the (−)−isomer. 4 The influence of morphine (120 μmol l−1) on papillary muscle AP was small. AP duration and FRP showed a marginal prolongation while V̇max was slightly decreased. 5 (−)−Naloxone 60 μmol l−1 had no effect on slow‐response APs of K+‐depolarized papillary muscles. Slow‐response APs were abolished by verapamil (1 μmol l−1). 6 In left atrial strips the prolongation of the AP duration produced by 120 μmol l−1 of either (−)− or (+)‐naloxone resembled the drug effect in papillary muscles. 7 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.