Abstract
DA-5018, a new capsaicin derivative, showed potent analgesic effect comparable to that of morphine in various experimental acute pain models. in this study, whether the analgesic mechanism of DA-5018 is related to opiate receptors or prostanoids was investigated. The affinity of DA-5018 for opiate receptor was determined by receptor binding assay. The Ki values of DA-5018 for nonspecific and specific $\mu$, $textsc{k}$, $\delta$-opiate receptor was 299$\pm$8.88, 735$\pm$215, 2930$\pm$ 163, 1550$\pm$813 nM, respectively and DA-5018 exhibited lower affinity than morphine. DA-5018 (10-"~3$\times$10-′M) inhibited electrically-evoked contractions of the guinea ply ileum and rat vas deferens, and these inhibition was not antagonized by naloxone(10 nM), an opiate receptor antagonist. Antagonism of analgesic effect of 7A-5018 by naloxone was examined by tail pinch test. Analgesic action of DA-5018(0.1 ~2 mg/kg, 5.c.) was not antagonized by naloxone(1 mg/rg, i.p.). These results indicate that pharmacological action of DA-5018 is not related with opiate receptor. Cyclooxygenase and 5-lipoxygenase activities in rat peritoneal neutrophil treated with A23187 and arachidonic acid were measured by radioimmunoassay. DA-5018 stimulated the cyclooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is not due to blocking opiate receptor or to inhibiting the synthesis of prostanoids in the arachidonic acid metabolism pathway.
