MIRFENTANIL ANTAGONIZES MORPHINE-INDUCED SUPPRESSION OF SPLENIC NK ACTIVITY IN MICE

Mirfentanil razinyl)-N-(1-phenethyl-4-piperidinyl)-2-furamide] was stu died for its antinociceptive and immunomodulatory effects in mice. Mir fentanil(1.0-32.0 mg/kg) increased tail-flick latency to a thermal sti mulus and this effect was antagonized (94 +/- 2%) by naltrexone (10.0 mg/kg). Unlike naltrexone, the delta opioid selective antagonist naltr indole (20.0 mg/kg) had no effect on mirfentanil-induced analgesia. In a dose-dependent fashion, the mu-selective antagonists beta-funaltrex amine (1.0-40.0 mg/kg) and naloxonazine (1.0-35.0 mg/kg) blocked mirfe ntanil(10.0 mg/kg)-induced analgesia up to 75% of the maximum analgesi c effect, Norbinaltorphimine (10.0 mg/kg) partially blocked (35%) the maximum analgesic effect following mirfentanil (10.0 mg/kg) administra tion. Single doses of mirfentanil (0.1-32.0 mg/kg) had no effect on sp lenic NK activity. However, preadministration of mirfentanil (1.0-10.0 mg/kg) blocked morphine-induced suppression of splenic NK activity. C ollectively, the results suggest that mirfentanil is a novel opioid th at induces antinociception predominately through mu opioid receptors b ut, unlike morphine or fentanyl, does not suppress splenic NK activity .