Interaction between the antinociceptive effect of ketoprofen and adrenergic modulatory systems

The interaction between the antinociceptive activity of ketoprofen and adre nergic agents was evaluated in the writhing test of mice. Dose-response cur ves were obtained for systemic and intrathecal antinociceptive effects of k etoprofen, phenylephrine, clonidine, desipramine, and prazosin; and ED50 we re calculated. The interactions were evaluated by isobolographic analysis o f the systemic or intrathecal co-administration of fixed-ratio combinations of ketoprofen with each adrenergic agent. The intraperitoneal combinations of ketoprofen with phenylephrine, clonidine, and prazosin showed supra-add itivity, indicating that activation of alpha (1) and alpha (2) adrenoceptor s play a role in nociceptive transmission at supraspinal levels. The same c ombinations given intrathecal were only additive. Desipramine intraperitone al was also supra-additive; however, when ketoprofen was administered intra thecally with desipramine, only an additive interaction was obtained. The s upra-additive interactions suggest that complementary mechanisms of antinoc iception have been activated, related with interference with the multiplici ty of receptors and systems involved in the transmission of the nociceptive information. Racemic. ketoprofen has an antinociceptive activity which is probably not only due to COX inhibition but also involves noradrenergic sys tems at spinal and supraspinal levels.