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

Abstract

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.

• Authors: S Lelas, L R Gerak, L K Landers, M R Brandt, J R Bagley, L L Brockunier, C P France
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 60 Issue 3 Pg. 665-75 (Jul 1998) ISSN: 0091-3057 [Print] United States
• PMID: 9678650 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Analgesics
• Narcotic Antagonists
• OHM10579
• Naltrexone
• Deuterium
• Nalbuphine
• mirfentanil
• Fentanyl

Topics

• Analgesics (pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Deuterium
• Discrimination, Psychological (drug effects)
• Dose-Response Relationship, Drug
• Female
• Fentanyl (analogs & derivatives, pharmacology)
• Macaca mulatta
• Male
• Nalbuphine (pharmacology)
• Naltrexone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Pain Measurement (drug effects)
• Respiratory Mechanics (drug effects)