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Anesthetic Potency of Nalbuphine and Interaction with Morphine in Rats

Cosmo A. DiFazio, PhD, MD^*, Jeffrey C. Moscicki, MS, and Michael R. Magruder, MD

*Professor of Anesthesiology. Department of Anesthesiology, University of Virginia Medical Center, Charlottesville, Virginia 22908. Research Specialist. Department of Anesthesiology, University of Virginia Medical Center, Charlottesville, Virginia 22908. Clinical Assistant Professor, University of Virginia Medical Center, and Staff Anesthesiologist, Andrews Air Force Base.

Abstract

The contribution to anesthesia by nalbuphine was determined in rats by measurement of the reduction in the anesthetic requirement for cyclopropane produced by increasing doses of nalbuphine while maintaining a constant level of anesthesia (MAC). The respiratory effect of nalbuphine was evaluated by measurement of arterial P_co2 at this constant MAC level. The response produced by the addition of morphine to a constant dose of nalbuphine in further reducing the cyclopropane anesthetic requirement was also evaluated, as was the effect on arterial Pco₂. The anesthetic contribution of nalbuphine was dose dependent until a plateau contribution of 0.22 MAC was achieved. Arterial Pco2 increased to a plateau level of 48 torr with nalbuphine administration from a Pco₂ of 41 torr with cyclopropane alone. Further increases in Pco₂ did not occur until exceedingly high nalbuphine doses were used. Morphine did not supplement the anesthetic contribution of nalbuphine, and there was no increase in Pco₂ when morphine was added to nalbuphine during cyclopropane anesthesia. These results suggest that nalbuphine produces analgesia by acting at kappa opioid receptors and that nalbuphine binds but produces minimal effects on mu opioid receptors within the central nervous system.

Key Words: ANALGESICS: nalbuphine, morphine • RECEPTORS: opioid

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999