buprenorphine and cyprodime

The use of regional and other opioid-sparing forms of anesthesia has been associated with a decrease in the recurrence of certain malignancies. Direct suppression of human natural killer cells by opioids has been postulated to explain this observation. However, the effect of different classes of opioids on suppression of natural killer cell cytotoxicity has not been systematically characterized.. After confirming that freshly isolated natural killer cells from peripheral human blood express opioid receptors, cells were incubated with increasing concentrations of clinically used or receptor-specific opioid agonists. We also evaluated the effect of pretreatment with receptor-specific antagonists or naloxone. Treated natural killer cells were then coincubated with a carboxyfluorescein succinimidyl ester-labeled target tumor cell line, K562. Annexin V staining was used to compare the percent of tumor cell apoptosis in the presence of opioid-pretreated and untreated natural killer cells. Treated samples were compared to untreated samples using Kruskal-Wallis tests with a post hoc Dunn correction.. Morphine, methadone, buprenorphine, loperamide, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin, and U-50488 significantly decreased natural killer cell cytotoxicity. When natural killer cells were pretreated with naloxone, cyprodime, and nor-binaltorphimine before exposure to morphine, there was no difference in natural killer cytotoxicity, compared to the amount observed by untreated natural killer cells. Fentanyl, O-desmethyltramadol, and [D-Pen2,D-Pen5] enkephalin did not change natural killer cell cytotoxicity compare to untreated natural killer cells.. Incubation of isolated natural killer cells with certain opioids causes a decrease in activity that is not observed after naloxone pretreatment. Suppression of natural killer cell cytotoxicity was observed with μ- and κ-receptor agonists but not δ-receptor agonists. These data suggest that the effect is mediated by μ- and κ-receptor agonism and that suppression is similar with many clinically used opioids.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics, Opioid; Anesthesia; Buprenorphine; Enkephalin, D-Penicillamine (2,5)-; Fentanyl; Fluoresceins; Humans; Immunosuppression Therapy; K562 Cells; Killer Cells, Natural; Loperamide; Methadone; Morphinans; Morphine; Naloxone; Naltrexone; Succinimides; Toll-Like Receptor 4; Tramadol

Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs. The effects of BPN were evaluated in the NIH test 24h post-administration in mice with genetic deletion of the MOR (Oprm1

Topics: Animals; Antidepressive Agents; Behavior, Animal; Buprenorphine; Feeding and Eating Disorders; Feeding Behavior; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphinans; Naltrexone; Narcotic Antagonists; Pain Measurement; Reaction Time; Receptors, Opioid, kappa; Receptors, Opioid, mu