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.
Babbedge
R C
RC
Biomedical Sciences Division, King's College, University of London, UK.
Hart
S L
SL
Moore
P K
PK
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D019323:omega-N-Methylarginine
D000700:Analgesics; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester