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l ‐N G ‐nitro arginine methyl ester exhibits antinociceptive activity in the mouse
Author(s) -
Moore P.K.,
Oluyomi A.O.,
Babbedge R.C.,
Wallace P.,
Hart S.L.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12153.x
Subject(s) - licking , chemistry , nociception , (+) naloxone , pharmacology , arginine , hyperalgesia , opioid , endocrinology , medicine , biochemistry , receptor , amino acid
1 l ‐N G ‐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.