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Selective inhibition of arachidonate 5‐lipoxygenase by novel acetohydroxamic acids: effects on acute inflammatory responses
Author(s) -
Higgs G.A.,
Follenfant R.L.,
Garland L.G.
Publication year - 1988
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.1476-5381.1988.tb11559.x
Subject(s) - chemistry , pharmacology , arachidonate 5 lipoxygenase , in vivo , lipoxygenase , subcutaneous injection , leukotriene b4 , hyperalgesia , eicosanoid , inflammation , endocrinology , medicine , biochemistry , enzyme , biology , arachidonic acid , nociception , receptor , microbiology and biotechnology
1 Two selective inhibitors of arachidonate 5‐lipoxygenase, BW A4C and BW A797C, have been studied for their effects on acute inflammatory responses following oral administration to rats and mice. 2 The concentrations of the lipoxygenase product leukotriene B 4 (LTB 4 ) in 6h inflammatory exudates, induced in rats by the subcutaneous implantation of carrageenin‐soaked polyester sponges, were reduced dose‐dependently by BW A4C (ED 50 = 2.6 mg kg −1 ) or BW A797C (ED 50 = 14.3 mg kg −1 ). 3 BW A4C and BW A797C had little or no effect on prostaglandin E 2 (PGE 2 ) concentrations in inflammatory exudates (ED 50 S > 100 mg kg −1 ). 4 Doses of up to 200 mg kg −1 of either BW A4C or BW A797C had no effect on carrageenin‐induced oedema in rat paws. 5 BW A4C and BW A797C had little or no effect on carrageenin‐induced hyperalgesia in rats or phenyl‐benzoquinone‐induced writhing in mice. 6 Yeast‐induced pyrexia in rats was reduced by both BW A4C (ED 50 = 32 mg kg −1 ) and BW A797C (ED 50 = 23 mg kg −1 ). 7 The accumulation of leucocytes in sponge exudates was reduced dose‐dependently by BW A4C (ED 50 = 54 mg kg −1 ) and BW A797C (ED 50 = 16.7 mg kg −1 ). 8 The selective lipoxygenase inhibitors BW A4C and BW A797C do not suppress inflammatory oedema or pain although they are anti‐pyretic and they do inhibit leucocyte migration. There is not, however, a close agreement between these in vivo activities and their potencies as lipoxygenase inhibitors.