Abstract |
L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol) was a potent inhibitor of leukotriene biosynthesis in intact rat and human leukocytes and CXBG mastocytoma cells (IC50 values, 18-240 nM) and of crude human leukocyte and highly purified porcine leukocyte 5-lipoxygenase (IC50 value, 4 X 10(-7) M). The selectivity of L-656,224 for 5-lipoxygenase was shown through the relative lack of activity of the compound on 12-lipoxygenase, 15-lipoxygenase, cyclooxygenase, catalase, and myeloperoxidase. The compound showed (i) oral activity against hyperalgesia induced in the rat paw by injection of yeast or platelet-activating factor, (ii) dyspnea in sensitized inbred rats induced by an aerosol of antigen, and (iii) bronchoconstriction induced by an aerosol of Ascaris in squirrel monkeys, suggesting a role for 5-lipoxygenase inhibitors in the treatment of asthma and peripheral pain.
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Authors | P Belanger, A Maycock, Y Guindon, T Bach, A L Dollob, C Dufresne, A W Ford-Hutchinson, P H Gale, S Hopple, C K Lau |
Journal | Canadian journal of physiology and pharmacology
(Can J Physiol Pharmacol)
Vol. 65
Issue 12
Pg. 2441-8
(Dec 1987)
ISSN: 0008-4212 [Print] Canada |
PMID | 2835137
(Publication Type: Journal Article)
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Chemical References |
- Benzofurans
- Lipoxygenase Inhibitors
- L 656224
- Catalase
- Peroxidase
- Arachidonate Lipoxygenases
- Prostaglandin-Endoperoxide Synthases
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Topics |
- Animals
- Arachidonate Lipoxygenases
(antagonists & inhibitors)
- Benzofurans
(pharmacology)
- Blood Platelets
(enzymology)
- Catalase
(antagonists & inhibitors)
- Cattle
- Cells, Cultured
- Eating
(drug effects)
- Female
- Humans
- Leukocytes
(enzymology)
- Lipoxygenase Inhibitors
- Neutrophils
(enzymology)
- Peroxidase
(metabolism)
- Prostaglandin-Endoperoxide Synthases
(metabolism)
- Rats
- Saimiri
- Soybeans
(enzymology)
- Species Specificity
- Swine
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