title: Effects of mu-, delta- and kappa-opioid antagonists in atrial preparations from nonfailing and failing human hearts.
abstract: 1. We examined the effects of naloxone (preferentially mu-antagonist), naltrindole (selective delta-antagonist) or nor-binaltorphimine (nor-BNI, selective kappa-antagonist) on auricular myocardium tissue from nonfailing and failing human hearts. 2. The opioid antagonists used in this study induced inhibitory effects in auricular strips from failing and nonfailing human hearts. In addition, the maximal effect, the IC50, and the slope of concentration-response curves obtained with mu-, delta-, and kappa-opioid antagonists were similar in failing and nonfailing human heart tissues. 3. The kappa-antagonist was more effective than naltrindole or naloxone. Moreover, the IC50 for nor-BNI (0.25 +/- 0.01 x 10(-5) M) was lower than the IC50 for naloxone (26.5 +/- 5.0 x 10(-5) M) and naltrindole (13.8 +/- 2.0 x 10(-5) M). Similar results were obtained in auricular strips from failing human hearts. 4. Our results demonstrate that the failing heart does not modify the inhibitory cardiac effects obtained with selective opioid antagonists.
authors.affiliation: Department of Anaesthesiology, University School of Medicine, CSV Arrixaca Hospital, Murcia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Llobel
authors.forename: M L
authors.initials: ML
authors.lastname: Laorden
mesh_terms: D000328:Adult; D000368:Aged; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects; D006349:Heart Valve Diseases / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
chemical_list: D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole