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. 1991 Mar;102(3):696–698. doi: 10.1111/j.1476-5381.1991.tb12235.x

Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.

Y Sarne 1, A Flitstein 1, E Oppenheimer 1
PMCID: PMC1917956  PMID: 1364840

Abstract

1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brasch H. Influence of the optical isomers (+)- and (-)-naloxone on beating frequency, contractile force and action potentials of guinea-pig isolated cardiac preparations. Br J Pharmacol. 1986 Aug;88(4):733–740. doi: 10.1111/j.1476-5381.1986.tb16245.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carratu' M. R., Mitolo-Chieppa D. Inhibition of ionic currents in frog node of Ranvier treated with naloxone. Br J Pharmacol. 1982 Sep;77(1):115–119. doi: 10.1111/j.1476-5381.1982.tb09276.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark C., Foreman M. I., Kane K. A., McDonald F. M., Parratt J. R. Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size. J Pharmacol Methods. 1980 Jun;3(4):357–368. doi: 10.1016/0160-5402(80)90077-7. [DOI] [PubMed] [Google Scholar]
  4. Fagbemi O., Leprán I., Parratt J. R., Szekeres L. Naloxone inhibits early arrhythmias resulting from acute coronary ligation. Br J Pharmacol. 1982 Aug;76(4):504–506. doi: 10.1111/j.1476-5381.1982.tb09246.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Frazier D. T., Ohta M., Narahashi T. Nature of the morphine receptor present in the squid axon. Proc Soc Exp Biol Med. 1973 Apr;142(4):1209–1214. doi: 10.3181/00379727-142-37210. [DOI] [PubMed] [Google Scholar]
  6. Huang X. D., Lee A. Y., Wong T. M., Zhan C. Y., Zhao Y. Y. Naloxone inhibits arrhythmias induced by coronary artery occlusion and reperfusion in anaesthetized dogs. Br J Pharmacol. 1986 Mar;87(3):475–477. doi: 10.1111/j.1476-5381.1986.tb10186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Iijima I., Minamikawa J., Jacobson A. E., Brossi A., Rice K. C. Studies in the (+)-morphinan series. 5. Synthesis and biological properties of (+)-naloxone. J Med Chem. 1978 Apr;21(4):398–400. doi: 10.1021/jm00202a018. [DOI] [PubMed] [Google Scholar]
  8. Lee A. Y., Unang T. W., Wong T. M. Prevention and reversal of ouabain-induced cardiotoxicity by naloxone in the guinea-pig. Clin Exp Pharmacol Physiol. 1986 Jan;13(1):55–58. doi: 10.1111/j.1440-1681.1986.tb00315.x. [DOI] [PubMed] [Google Scholar]
  9. Merz H., Langbein A., Stockhaus K., Walther G., Wick H. Structure-activity relationships in narcotic antagonists with N-furylmethyl substituents. Adv Biochem Psychopharmacol. 1973;8(0):91–107. [PubMed] [Google Scholar]
  10. Parratt J. R., Sitsapesan R. Stereospecific antiarrhythmic effect of opioid receptor antagonists in myocardial ischaemia. Br J Pharmacol. 1986 Apr;87(4):621–622. doi: 10.1111/j.1476-5381.1986.tb14577.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sarne Y., Hochman I., Eshed M., Oppenheimer E. Antiarrhythmic action of naloxone: direct, non-opiate effect on the rat heart. Life Sci. 1988;43(10):859–864. doi: 10.1016/0024-3205(88)90513-9. [DOI] [PubMed] [Google Scholar]

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