TY - JOUR
T1 - OHM3295
T2 - A fentanyl-related 4-Heteroanilido piperidine with analgesic effects but not suppressive effects on splenic NK activity in mice
AU - Carr, Daniel J.J.
AU - Baker, Marc L.
AU - Holmes, Charles
AU - Brockunier, Linda L.
AU - Bagley, Jerome R.
AU - France, Charles P.
N1 - Funding Information:
Acknowledgements -- This work was supported by grants from The Cancer Association of Greater New Orleans (DJJC), The LSU Neuroscience Center Incentive Grants Program (DJJC and CPF) and USPHS Grant DA-05018 (CPF). CPF is the recipient of a Research Scientist Development Award from the National Institute on Drug Abuse (DA00211). Animals used in these studies were maintained in accordance with the Institutional Animal Care and Use Committee, Louisiana State University Medical Center, and the guidelines of thc Committee on Care and Use of Laboratory Animals Resources, National Research Council, Department of Health, Education, and Welfare Publications Number (National Institutes of Health) 85-23, Revised 1985.
PY - 1994/10
Y1 - 1994/10
N2 - 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.
AB - 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.
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U2 - 10.1016/0192-0561(94)90057-4
DO - 10.1016/0192-0561(94)90057-4
M3 - Article
C2 - 7843855
AN - SCOPUS:0028152489
SN - 0192-0561
VL - 16
SP - 835
EP - 844
JO - International Journal of Immunopharmacology
JF - International Journal of Immunopharmacology
IS - 10
ER -