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 mu-selective antagonists beta-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 mu opioid receptors but, unlike morphine or fentanyl, does not suppress splenic NK activity.
Carr
D J
DJ
Department of Microbiology, Immunology, Parasitology, Louisiana State University Medical Center, New Orleans 70112-1393, USA. dcarr@pop3.lsumc.edu
Brockunier
L L
LL
Scott
M
M
Bagley
J R
JR
France
C P
CP
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000700:Analgesics; D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; C069209:mirfentanil; D005283:Fentanyl