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.
Carr
D J
DJ
Department of Microbiology, LSU Neuroscience Center, Louisiana State University Medical Center, New Orleans 70112-1393.
Baker
M L
ML
Holmes
C
C
Brockunier
L L
LL
Bagley
J R
JR
France
C P
CP
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology; D013154:Spleen / Q000276:immunology
D000700:Analgesics; D007166:Immunosuppressive Agents; C091795:OHM 3295; D009271:Naltrexone; D005283:Fentanyl