ANTINOCICEPTIVE 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-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 mug) and L-N(G)-nitro arginine base (L-NOARG; 10 mug) but not D-NAME (10 mug) were also anti-nociceptive following intracerebroventricular administration. L-NAME (10 ug) administered by this route did not influence locomotor activity. L-NMMA was inactive at doses up to 40 mug by this route. At higher doses (75-200 mug) L-NMMA produced a similar and non-dose related reduction in early/late phase paw-licking time. D-NMMA (100 mug) 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.