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 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.