MODULATION OF NITRIC-OXIDE EFFECTS BY FLURBIPROFEN ENANTIOMERS AND NEFOPAM AND ITS RELATION TO ANTINOCICEPTION

We have examined the interactions of the analgesics, R- and S-flurbipr ofen and nefopam, with nitric oxide (NO) in several experimental syste ms. Phenylephrine-precontracted rat aortic strips with intact endothel ium were relaxed by R- and S-flurbiprofen and nefopam in a concentrati on-dependent manner. Removal of endothelium, inhibition of guanylate c yclase, inhibition of NO biosynthesis and inactivation of NO significa ntly reduced these relaxations. R- and S-flurbiprofen as well as nefop am enhanced the inhibition of platelet aggregation caused by rat perit oneal neutrophils or 3-morpholinosydnonimine. The antinociceptive effe cts of R- and S-flurbiprofen in the mouse writhing test as well as tho se of nefopam in the hot plate test were not significantly affected by administration of NO synthase inhibitors. We conclude that the increa se in the biological activity of NO by R- and S-flurbiprofen and nefop am does not play a major role in the antinociceptive activity of the d rugs, but might contribute to acute hypotension, a side-effect occasio nally seen with flurbiprofen and nefopam.