Comparative cardiac contractile actions of six narcotic analgesics: Morphine, meperidine, pentazocine, fentanyl, methadone and l-α-acetylmethadol (LAAM)

S. V. Rendig, Ezra A Amsterdam, G. L. Henderson, D. T. Mason

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Abstract

Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-α-acetylmethadol), at concentrations from 10-8 to 10-4 M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10-8 to 10-6 M except for small but significant (P<.05) increases in all three parameters at 10-6 M fentanyl, and small but significant increases in dT/dt at 10-8 to 10-6 M meperidine. At 10-5M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-α-acetylmethadol (-11%). For all six narcotics, the 10-4 M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10-4 M) did not prevent this reduction of contractile performance except at the highest concentration (10-4 M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-α-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 x 10-7 M) elicited a positive inotropic response whether administered in the presence of 10-4 M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and decreased muscle excitability are consistent with the hypothesis that narcotic analgesics in high concentrations exert a nonspecific, local anesthetic effect on the myocardium.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume215
Issue number1
StatePublished - 1980

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Methadyl Acetate
Pentazocine
Meperidine
Methadone
Narcotics
Fentanyl
Morphine
Muscles
Naloxone
Isoproterenol
Myocardium
Pharmaceutical Preparations
Narcotic Antagonists
Papillary Muscles
Anti-Arrhythmia Agents
Opioid Receptors
Local Anesthetics
Electric Stimulation
Anesthetics
Cats

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{a3c4afefa85e4a89b282aa174c2e5eee,
title = "Comparative cardiac contractile actions of six narcotic analgesics: Morphine, meperidine, pentazocine, fentanyl, methadone and l-α-acetylmethadol (LAAM)",
abstract = "Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-α-acetylmethadol), at concentrations from 10-8 to 10-4 M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10-8 to 10-6 M except for small but significant (P<.05) increases in all three parameters at 10-6 M fentanyl, and small but significant increases in dT/dt at 10-8 to 10-6 M meperidine. At 10-5M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7{\%}), but significantly reduced in muscles exposed to pentazocine (-8{\%}) or l-α-acetylmethadol (-11{\%}). For all six narcotics, the 10-4 M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10-4 M) did not prevent this reduction of contractile performance except at the highest concentration (10-4 M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97{\%} of control T), except in l-α-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 x 10-7 M) elicited a positive inotropic response whether administered in the presence of 10-4 M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and decreased muscle excitability are consistent with the hypothesis that narcotic analgesics in high concentrations exert a nonspecific, local anesthetic effect on the myocardium.",
author = "Rendig, {S. V.} and Amsterdam, {Ezra A} and Henderson, {G. L.} and Mason, {D. T.}",
year = "1980",
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volume = "215",
pages = "259--265",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
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T1 - Comparative cardiac contractile actions of six narcotic analgesics

T2 - Morphine, meperidine, pentazocine, fentanyl, methadone and l-α-acetylmethadol (LAAM)

AU - Rendig, S. V.

AU - Amsterdam, Ezra A

AU - Henderson, G. L.

AU - Mason, D. T.

PY - 1980

Y1 - 1980

N2 - Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-α-acetylmethadol), at concentrations from 10-8 to 10-4 M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10-8 to 10-6 M except for small but significant (P<.05) increases in all three parameters at 10-6 M fentanyl, and small but significant increases in dT/dt at 10-8 to 10-6 M meperidine. At 10-5M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-α-acetylmethadol (-11%). For all six narcotics, the 10-4 M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10-4 M) did not prevent this reduction of contractile performance except at the highest concentration (10-4 M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-α-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 x 10-7 M) elicited a positive inotropic response whether administered in the presence of 10-4 M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and decreased muscle excitability are consistent with the hypothesis that narcotic analgesics in high concentrations exert a nonspecific, local anesthetic effect on the myocardium.

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