Selective inhibition of arachidonate 5‐lipoxygenase by novel acetohydroxamic acids: effects on acute inflammatory responses

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Abstract
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 B4 (LTB4) in 6h inflammatory exudates, induced in rats by the subcutaneous implantation of carrageenin-soaked polyester sponges, were reduced dose-dependently by BW A4C (ED50 = 2.6 mg kg−1) or BW A797C (ED50 = 14.3 mg kg−1). 3 BW A4C and BW A797C had little or no effect on prostaglandin E2 (PGE2) concentrations in inflammatory exudates (ED50S > 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 (ED50 = 32 mg kg−1) and BW A797C (ED50 = 23 mg kg−1). 7 The accumulation of leucocytes in sponge exudates was reduced dose-dependently by BW A4C (ED50 = 54 mg kg−1) and BW A797C (ED50 = 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.