L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse.
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 microgram 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 microgram per mouse) in 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 (600mgkg 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.
Moore
P K
PK
Smooth Muscle Pharmacology Group, King's College, University of London.
Oluyomi
A O
AO
Babbedge
R C
RC
Wallace
P
P
Hart
S L
SL
D000284:Administration, Oral; D000700:Analgesics; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005557:Formaldehyde; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control
D000700:Analgesics; D005557:Formaldehyde; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester