Mirfentanil antagonizes morphine-induced suppression of splenic NK activity in mice

Mirfentanil [N-(2-pyrazinyl)-N-(1-phenethyl-4-piperidinyl)-2-furamide] was studied for its antinociceptive and immunomodulatory effects in mice. Mirfentanil (1.0–32.0 mg/kg) increased tail-flick latency to a thermal stimulus and this effect was antagonized (94 ± 2%) by naltrexone (10.0 mg/kg). Unlike naltrexone, the delta opioid selective antagonist naltrindole (20.0 mg/kg) had no effect on mirfentanil-induced analgesia. In a dose-dependent fashion, the μ-selective antagonists β-funaltrexamine (1.0–40.0 mg/kg) and naloxonazine (1.0–35.0 mg/kg) blocked mirfentanil (10.0 mg/kg)-induced analgesia up to 75% of the maximum analgesic effect. Norbinaltorphimine (10.0 mg/kg) partially blocked (35%) the maximum analgesic effect following mirfentanil (10.0 mg/kg) administration. Single doses of mirfentanil (0.1–32.0 mg/kg) had no effect on splenic NK activity. However, preadministration of mirfentanil (1.0–10.0 mg/kg) blocked morphine-induced suppression of splenic NK activity. Collectively, the results suggest that mirfentanil is a novel opioid that induces antinociception predominately through μ opioid receptors but, unlike morphine or fentanyl, does not suppress splenic NK activity.