Pharmacological profile of a deuterium-substituted mirfentanil derivative, OHM10579, in rhesus monkeys.

The discriminative-stimulus, respiratory, and antinociceptive effects of OHM10579, an isotopic isomer of mirfentanil, were characterized in rhesus monkeys. In monkeys discriminating nalbuphine, 0.32 mg/kg of OHM10579 partially substituted for nalbuphine. In monkeys treated daily with 3.2 mg/kg of morphine and discriminating 0.01 mg/kg of naltrexone, 0.32 mg/kg of OHM10579 substituted for naltrexone. In morphine-abstinent monkeys, morphine reversed naltrexone-lever responding, an effect attenuated by OHM10579. The shift to the right in the morphine dose-effect curve was greater 2 h after 0.32 mg/kg of OHM10579 compared to 0.32 mg/kg of mirfentanil, indicating that OHM10579 has a longer duration of action than mirfentanil. In a warm-water tail-withdrawal procedure, 10 and 17.8 mg/kg of OHM10579 had antinociceptive effects that were not antagonized by naltrexone. Morphine decreased breathing in air to 48%, whereas the maximal decrease with OHM10579 was to 75% of control. OHM10579 attenuated hyperventilation induced by 5% CO2 and partially antagonized the respiratory-depressant effects of morphine. OHM10579 can be classified as a low-efficacy mu-opioid agonist with some nonopioid actions. These results indicate that the pharmacology of the mirfentanil isotope OHM10579 is similar to that of mirfentanil, but that OHM10579 might have a longer duration of action.