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

The anti-nociceptive effect of selective inhibitors of nitric oxide synthase has been assessed in a formalin-induced paw-licking model in mice. L-NG-Nitro arginine methyl ester (L-NAME) but not L-NG-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 micrograms) and L-NG-nitro arginine base (L-NOARG; 10 micrograms) but not D-NAME (10 micrograms) were also anti-nociceptive following intracerebroventricular administration. L-NAME (10 micrograms) administered by this route did not influence locomotor activity. L-NMMA was inactive at doses up to 40 micrograms by this route. At higher doses (75-200 micrograms) L-NMMA produced a similar and non-dose related reduction in early/late phase paw-licking time. D-NMMA (100 micrograms) 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.