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

Snjezana Lelas, Lisa R. Gerak, Laura K. Landers, Michael R. Brandt, Jerome R. Bagley, Linda L. Brockunier, Charles P. France

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 μ-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.

Original languageEnglish (US)
Pages (from-to)665-675
Number of pages11
JournalPharmacology Biochemistry and Behavior
Volume60
Issue number3
DOIs
StatePublished - Jun 1 1998

Keywords

  • Antinociception
  • Drug discrimination
  • Mirfentanil
  • OHM10579
  • Respiration
  • Rhesus monkey

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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