Myocardial opiate receptor activity is stereospecific, independent of muscarinic receptor antagonism, and may play a role in depressing cardiac function.
Earlier work has shown that morphine sulfate can produce a dose-related decrease in heart rate (HR) and cardiac output (CO) in isolated working rat hearts. This response is preventable with the use of the opiate receptor antagonist, naloxone hydrochloride. In this study, the stereospecificity of the opiate response was tested with the use of levorphanol tartrate and its d-isomer, dextrorphan, in our Langendorff rat heart model. The interaction of muscarinic receptor activity with the opiate response was tested by first adding bethanechol chloride to the perfusate in the presence and absence of atropine (5 X 10(-9) mmol/L). Our earlier studies with morphine sulfate were then repeated in the presence of the same concentration of atropine. At a concentration of 5 X 10(-6) mmol/L, levorphanol tartrate produced a significant decrease in CO (p less than 0.05), while a similar concentration of dextrorphan produced little change in either HR or CO. Bethanechol chloride, in a concentration of 3 X 10(-6) mmol/L, produced a significant decrease in HR and CO (p less than 0.05), which was prevented by atropine. When morphine sulfate was added to the standard perfusate (3 X 10(-4) mmol/L), HR and CO were significantly decreased (p less than 0.05). This change was not prevented by the addition of atropine. The opiate effect on myocardial function is mediated by a stereospecific opiate receptor, which acts independently of muscarinic receptor antagonism.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D003917:Dextrorphan / Q000494:pharmacology; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007981:Levorphanol / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D018727:Muscarinic Antagonists; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D013237:Stereoisomerism
D001626:Bethanechol Compounds; D018727:Muscarinic Antagonists; D011957:Receptors, Opioid; D018723:Bethanechol; D003917:Dextrorphan; D007981:Levorphanol; D009020:Morphine; D001285:Atropine