OHM3295: A fentanyl-related 4-Heteroanilido piperidine with analgesic effects but not suppressive effects on splenic NK activity in mice

Daniel J.J. Carr, Marc L. Baker, Charles Holmes, Linda L. Brockunier, Jerome R. Bagley, Charles P. France

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The immunoregulatory effects of fentanyl and a fentanyl-related compound, OHM3295, were studied in mice. Male CD1 mice treated with a range of fentanyl doses (0.1-1.0 mg/kg, subcutaneously) showed suppression of splenic natural killer (NK) activity following 0.25-0.50 mg/kg fentanyl dose but not higher (0.75-1.0 mg/kg) or lower (0.1 mg/kg) doses. Fentanyl (0.01-32.0 mg/kg) also induced dose-related analgesia as measured by an increase in tail flick latency; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). Pretreatment with naltrexone (1.0-3.2 mg/kg) resulted in significant suppression of splenic NK activity following fentanyl (10.0-32.0 mg/kg) administration. In comparison to fentanyl, OHM3295 (3.2-25.0 mg/kg) augmented splenic NK activity in a naltrexone-reversible manner. Similar to fentanyl, OHM3295 (1.0-32.0 mg/kg) also induced a naltrexone-sensitive, dose-related analgesia as measured by an increase in tail flick latency. These results with OHM3295 demonstrate a novel profile of effects which includes naltrexone-sensitive analgesic effects in the absence of immunosuppressive effects. In addition, this is the first reported case in which a compound with opioid analgesic effects has been shown to potentiate natural killer cytolytic activity following in vivo administration.

Original languageEnglish (US)
Pages (from-to)835-844
Number of pages10
JournalInternational Journal of Immunopharmacology
Volume16
Issue number10
DOIs
StatePublished - Oct 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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