Evidence for the participation of the nitric oxide-cyclic GMP pathway in the antinociceptive action of meloxicam in the formalin test.
The involvement of the nitric oxide-cyclic GMP pathway in the antinociceptive action of the cyclooxygenase-2 preferential inhibitor meloxicam was assessed in the rat formalin test. Rats received local pretreatment with saline or meloxicam and then 50 microl of dilute formalin (1%). Local administration of meloxicam produced a dose-dependent antinociception in the second phase of the formalin test. The antinociception produced by meloxicam was due to a local action as its administration in the contralateral paw was ineffective. Local pretreatment of the paws with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not affect the antinociception produced by meloxicam. However, N(G)-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor) or 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) blocked in a dose-dependent way the effect of meloxicam. It is concluded that the peripheral antinociceptive effect of meloxicam involves a local NO-cyclic GMP pathway.
Aguirre-Bañuelos
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P
Sección de Terapéutica Experimental, Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 22026, 14000, México, D.F., Mexico.
Granados-Soto
V
V
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D000077239:Meloxicam; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D018712:Analgesics, Non-Narcotic; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D013843:Thiazines; D013844:Thiazoles; D005557:Formaldehyde; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D000077239:Meloxicam