Effect of CI-922, a potential new antiallergy agent, on arachidonic acid metabolism in vitro.
CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo[3,2-b]indole-2- carboxamide, 1,2-ethanediamine, 2:1), an antiallergy compound, was tested for its effects on arachidonic acid metabolism, and its potency was compared to that of proxicromil, BW-755C, indomethacin, and nordihydroguaiaretic acid (NDGA). CI-922 was both a relatively potent and selective inhibitor of 5-HETE and LTB4 formation in human leukocytes, being equipotent to BW-755C and about four-fold more potent than proxicromil. However, CI-922 was rather weak in inhibiting the formation of PGE2 in bovine seminal vesicles. The parallel inhibition of 5-HETE and LTB4 formation by CI-922 suggests that either direct or indirect inhibition of the 5-lipoxygenase pathway may explain, at least in part, its antiallergy properties.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000328:Adult; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001393:Azoles / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012669:Seminal Vesicles / Q000201:enzymology; D013777:Tetrazoles / Q000494:pharmacology*
D001095:Arachidonic Acids; D001393:Azoles; D006893:Hydroxyeicosatetraenoic Acids; D007211:Indoles; D011720:Pyrazoles; D013777:Tetrazoles; D016718:Arachidonic Acid; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C045584:CI 922; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D001094:Arachidonate 5-Lipoxygenase; D007213:Indomethacin