Anti-nociceptive activity of nitric oxide synthase inhibitors in the mouse: dissociation between the effect of l-NAME and l-NMMA

Abstract— The anti-nociceptive effect of selective inhibitors of nitric oxide synthase has been assessed in a formalin-induced paw-licking model in mice. l -N^G-Nitro arginine methyl ester (l -NAME) but not l -N^G-monomethyl arginine (l -NMMA) exhibited anti-nociceptive activity in both the early and late phases of paw licking following intraperitoneal administration. The effect on the late phase response was more pronounced. l -NAME (0·1–100 μg) and l -N^G-nitro arginine base (l -NOARG; 10 μg) but not d -NAME (10 μg) were also anti-nociceptive following intracerebroventricular administration. l -NAME (10 μg) administered by this route did not influence locomotor activity. l -NMMA was inactive at doses up to 40 μg by this route. At higher doses (75–200 μg) l -NMMA produced a similar and non-dose related reduction in early/late phase paw-licking time. d -NMMA (100 μg) was inactive. The greater anti-nociceptive effect of l -NAME in this model accords with recently published biochemical data indicating that l -NAME is several orders of magnitude more potent than l -NMMA as an inhibitor of brain nitric oxide synthase. These data support the use of l -NAME as a selective tool to investigate the central pharmacological effects of nitric oxide.