Evidence for the participation of the nitric oxide-cyclic GMP pathway in the antinociceptive effect of nimesulide.
The involvement of the nitric oxide-cyclic GMP pathway in the peripheral antinociception induced by the COX-2 preferential inhibitor nimesulide was assessed by using the formalin test in the rat. Intraplantar administration of nimesulide in the formalin-injured paw produced a significant antinociceptive effect that was due to a local action, because nimesulide administration in the contralateral paw was ineffective. Local pretreatment of the paws with saline or N(G)-D-nitro-arginine methyl ester (D-NAME, the inactive isomer of L-NAME) did not affect the antinociception produced by nimesulide. However, local administration of L-NAME (a nitric oxide synthesis inhibitor) or 1H-(1,2,4)-oxadiazolo(4, 2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) blocked the effect of nimesulide. Moreover, the antinociceptive effect of local nimesulide was potentiated by the coadministration of 3-morpholino-sydnonimine-HCl (SIN-1, a nitric oxide donor). It is concluded that nimesulide produces antinociception by a peripheral mechanism of action requiring activation of the nitric oxide-cyclic GMP pathway at the local level.
Facultad de Ciencias Químicas, Benemérita Universidad de Puebla, Mexico.
M
M
Islas-Cadena
P
P
Aguirre-Bañuelos
V
V
Granados-Soto
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006152:Cyclic GMP / Q000502:physiology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D006152:Cyclic GMP; C012655:nimesulide; D019331:NG-Nitroarginine Methyl Ester