OHM3295 - A FENTANYL-RELATED 4-HETEROANILIDO PIPERIDINE WITH ANALGESIC EFFECTS BUT NOT SUPPRESSIVE EFFECTS ON SPLENIC NK ACTIVITY IN MICE

The immunoregulatory effects of fentanyl and a fentanyl-related compou nd, OHM3295, were studied in mice. Male CD1 mice treated with a range of fentanyl doses (0.1-1.0 mg/kg, subcutaneously) showed suppression o f splenic natural killer (NK) activity following 0.25-0.50 mg/kg fenta nyl dose but not higher (0.75-1.0 mg/kg) or lower (0.1 mg/kg) doses. F entanyl (0.01-32.0 mg/kg) also induced dose-related analgesia as measu red by an increase in tail flick latency; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). Pretreatment with naltrex one (1.0-3.2 mg/kg) resulted in significant suppression of splenic NK activity following fentanyl (10.0-32.0 mg/kg) administration. In compa rison to fentanyl, OHM3295 (3.2-25.0 mg/kg) augmented splenic NK activ ity in a naltrexone-reversible manner. Similar to fentanyl, OHM3295 (1 .0-32.0 mg/kg) also induced a naltrexone-sensitive, dose-related analg esia as measured by an increase in tail flick latency. These results w ith OHM3295 demonstrate a novel profile of effects which includes nalt rexone-sensitive analgesic effects in the absence of immunosuppressive effects. In addition, this is the first reported case in which a comp ound with opioid analgesic effects has been shown to potentiate natura l killer cytolytic activity following in vivo administration.