title: The antinociceptive effect of 1-(2-trifluoromethylphenyl) imidazole (TRIM), a potent inhibitor of neuronal nitric oxide synthase in vitro, in the mouse.
abstract: 1-(2-trifluoromethylphenyl)imidazole (TRIM) is a potent inhibitor of neuronal (mouse cerebellar) and inducible (lung from endotoxin-pretreated rats) isoforms of nitric oxide synthase (NOS) with IC50 values of 28.2 microM and 27.0 microM, respectively. In contrast, TRIM is a poor inhibitor of bovine aortic endothelial NOS with an IC50 of 1057.5 microM. TRIM (10-50 mg kg-1) administered i.p. exhibits dose-related antinociceptive activity in the mouse (assessed as inhibition of late phase formalin-induced hindpaw licking behaviour) with an ED50 of 85.8 mumol kg-1. In contrast, TRIM (50 mg kg-1, i.p.) failed to influence mean arterial blood pressure in the urethane-anaesthetized mouse. Thus, TRIM may be of use as an experimental tool with which to investigate the biological roles of nitric oxide (NO) within the central nervous system.
authors.affiliation: Biomedical Sciences Division, King's College, University of London.
authors.forename: R L
authors.initials: RL
authors.lastname: Handy
authors.forename: P
authors.initials: P
authors.lastname: Wallace
authors.forename: Z A
authors.initials: ZA
authors.lastname: Gaffen
authors.forename: K J
authors.initials: KJ
authors.lastname: Whitehead
authors.forename: P K
authors.initials: PK
authors.lastname: Moore
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D007093:Imidazoles; C098186:1-(2-trifluoromethylphenyl)imidazole; D019001:Nitric Oxide Synthase