l‐NG‐nitro arginine methyl ester exhibits antinociceptive activity in the mouse

Open Access
Publisher Website
Google Scholar
Abstract
1 l-NG-nitro arginine methyl ester (l-NAME, 1–75 mg kg−1) administered intraperitoneally (i.p.) elicits dose-related antinociception in the mouse assessed by the formalin-induced paw licking procedure. Antinociceptive activity is still present 24 h after injection. l-NAME (75 mg kg−1, i.p.) is also antinociceptive in the acetic acid-induced abdominal constriction and hot plate procedures. 2 l-NAME additionally produces a dose-related inhibition of formalin-induced paw licking following intracerebroventricular (i.c.v., 0.1–100 μg per mouse) and oral (p.o., 75–150 mg kg−1) administration. 3 l-Arginine (600 mg kg−1, i.p.) but not d-arginine (600 mg kg−1) or naloxone (5 mg kg−1) reverses the antinociceptive effect of l-NAME in the formalin test. 4 High doses of l-NAME (37.5–600 mg kg−1) but not d-NAME (75 mg kg−1) administered i.p. produce dose-related increases in blood pressure of the urethane-anaesthetized mouse whilst i.c.v. injected l-NAME (0.1 and 100 μg per mouse) is inactive. 5 l-NAME (75 mg kg−1, i.p.) did not inhibit oedema formation in the formalin-injected mouse hindpaw. 6 l-NAME (75 mg kg−1) did not produce any overt behavioural changes in treated mice and failed to influence locomotor activity or the incidence of dipping, crossing, rearing or circling behaviour assessed by a modified ‘head-dipping’ board procedure. A high dose of l-NAME (600 mg kg−1) reduced dipping behaviour and locomotor activity suggesting a possible sedative effect. d-NAME (600 mg kg−1) was inactive. 7 These results suggest that l-NAME produces an opioid-independent and long-lasting antinociception in the mouse most probably by a direct effect within the central nervous system.