Anesthetic Potency of Nalbuphine and Interaction with Morphine in Rats

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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 Pco2 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.