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The antinociceptive effect of 1‐(2‐trifluoromethylphenyl) imidazole (TRIM), a potent inhibitor of neuronal nitric oxide synthase in vitro , in the mouse
Author(s) -
Handy Rachel L.C.,
Wallace P.,
Gaffen Z.A.,
Whitehead K.J.,
Moore P.K.
Publication year - 1995
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.1476-5381.1995.tb15078.x
Subject(s) - nitric oxide synthase , nitric oxide , ed50 , pharmacology , nociception , chemistry , licking , endocrinology , medicine , in vitro , biochemistry , biology , receptor
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 IC 50 values of 28.2 μ m and 27.0 μ m , respectively. In contrast, TRIM is a poor inhibitor of bovine aortic endothelial NOS with an IC 50 of 1057.5 μ m . 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 ED 50 of 85.8 μmol 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.