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.
Department of Microbiology, LSU Neuroscience Center, Louisiana State University Medical Center, New Orleans 70112-1393.
D J
DJ
Carr
M L
ML
Baker
C
C
Holmes
L L
LL
Brockunier
J R
JR
Bagley
C P
CP
France
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