Pharmacology of the dual inhibitor of cyclooxygenase and 5-lipoxygenase 3-hydroxy-5-trifluoromethyl-N-(2-(2-thienyl)-2-phenyl-ethenyl)-benzo (b)thiophene-2-carboxamide.

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作者: Luell, S ; Bach, T ; Bailey, P J ; Anderson, R L ; Dallob, A L ; Meurer, R ; Allison, D L ; Durette, P L ; Hopple, S L ; Hand, K M

3-Hydroxy-5-trifluoromethyl-N-(2-(2-thienyl)-2-phenyl-ethenyl)- benzo (b) thiophene-2-carboxamide (L-652,343) is an inhibitor of cyclooxygenase and 5-lipoxygenase in vitro and inhibits the synthesis of the products of both these pathways in whole cells. L-652,343 is an inhibitor of the acute edema induced by carrageenan in vivo and is active topically in suppressing arachidonic acid induced inflammation in the skin. The compound is an effective inhibitor of the chronic inflammation of adjuvant and type II collagen induced polyarthritis. L-652,343 is an extremely potent analgesic in models of yeast and platelet activating factor induced hyperalgesia in rats and phenylbenzoquinone-induced writhing in mice. The fever induced by Brewer's yeast is lowered by L-652,343. The ulcerogenicity and gastric bleeding induced by L-652,343 is extremely low, providing a favorable therapeutic index which is superior to that of indomethacin, piroxicam and phenylbutazone.

1987-10-01·Biochemical Pharmacology2区 · 医学

L-652,343, a novel dual cyclo/lipoxygenase inhibitor, inhibits LTB4-production by stimulated human polymorphonuclear cells but not by stimulated human whole blood

2区 · 医学

Article

作者: Deckmyn, H. ; Arnout, J. ; Vermylen, J. ; Gresele, P.

L-652,343 (I) concentration-dependently inhibited LTB₄ formation by isolated, purified human polymorphonuclear leukocytes stimulated by A23187 (50% inhibitory concentration = 1.4 μM).However, I was inactive in A23187-stimulated whole blood (≤10^-3 M).The absence of activity appeared to be due to I binding to blood proteins.The loss of activity of blood was confined to the 5-lipopxygenase-inhibitory effect; in stimulated whole flood, I continued to inhibit TXB₂ formation, indicating persistence of blocking activity of platelet cyclooxygenase.

1986-01-01·Advances in prostaglandin, thromboxane, and leukotriene research

L-652,343: a novel dual 5-lipoxygenase/cyclooxygenase inhibitor.

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