OHM3295 - A FENTANYL-RELATED 4-HETEROANILIDO PIPERIDINE WITH ANALGESIC EFFECTS BUT NOT SUPPRESSIVE EFFECTS ON SPLENIC NK ACTIVITY IN MICE

被引:10
作者
CARR, DJJ
BAKER, ML
HOLMES, C
BROCKUNIER, LL
BAGLEY, JR
FRANCE, CP
机构
[1] LOUISIANA STATE UNIV,MED CTR,CTR NEUROSCI,DEPT PHARMACOL,NEW ORLEANS,LA 70112
[2] OHMEDA INC,MURRAY HILL,NJ
来源
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY | 1994年 / 16卷 / 10期
关键词
D O I
10.1016/0192-0561(94)90057-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:835 / 844
页数:10
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