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-flurbiprofen and nefopam, with nitric oxide (NO) in several experimental systems. Phenylephrine-precontracted rat aortic strips with intact endothelium were relaxed by R- and S-flurbiprofen and nefopam in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase, inhibition of NO biosynthesis and inactivation of NO significantly reduced these relaxations. R- and S-flurbiprofen as well as nefopam enhanced the inhibition of platelet aggregation caused by rat peritoneal neutrophils or 3-morpholinosydnonimine. The antinociceptive effects of R- and S-flurbiprofen in the mouse writhing test as well as those of nefopam in the hot plate test were not significantly affected by administration of NO synthase inhibitors. We conclude that the increase in the biological activity of NO by R- and S-flurbiprofen and nefopam does not play a major role in the antinociceptive activity of the drugs, but might contribute to acute hypotension, a side-effect occasionally seen with flurbiprofen and nefopam.
Pallapies
D
D
Department of Pharmacology and Toxicology, Ruhr-Universität, Bochum, Germany.
Peskar
B A
BA
Brune
K
K
Zeilhofer
H U
HU
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005480:Flurbiprofen / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009340:Nefopam / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014661:Vasoconstriction / Q000187:drug effects
D000700:Analgesics; D009569:Nitric Oxide; D009340:Nefopam; D005480:Flurbiprofen; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester