Effect of caffeine coadministration and of nitric oxide synthesis inhibition on the antinociceptive action of ketorolac.
The effects of caffeine and nitric oxide synthesis inhibition on the antinociceptive action of ketorolac were assessed using the pain-induced functional impairment model in the rat. Nociception was induced by the intra-articular injection of uric acid. Ketorolac, but not caffeine, produced an antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of this potentiation. The results suggest the participation of the L-arginine-nitric oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced antinociception.
López-Muñoz
F J
FJ
Departamento de Farmacología y Toxicologia, Estudios Avanzados del Instituto Politécnico Nacional, Apartado, México, D.F., Mexico.
Castañeda-Hernández
G
G
Flores-Murrieta
F J
FJ
Granados-Soto
V
V
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020910:Ketorolac; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D002110:Caffeine; D014046:Tolmetin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D020910:Ketorolac