title: CI-922--a novel, potent antiallergic compound--I. Inhibition of mediator release in vitro.
abstract: CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo[3,2-b]-indole- 2-carboxamide, L-arginine salt) is a novel antiallergy compound which inhibits the release of the inflammatory mediators histamine and leukotriene (LT) from stimulated cells. CI-922 showed potent, effective inhibition of antigen-induced mediator release from human basophils and isolated guinea pig lung. The drug inhibited ragweed or housedust-induced histamine release from basophils of allergic human donors (IC50 = 8.6 microM). The antiallergy agents proxicromil (IC50 = 80 microM) and cromolyn (100 microM) were less potent than CI-922 or inactive, respectively. In fragmented lung from actively sensitized guinea pigs, CI-922 (IC50 = 1.5 microM), blocked the antigen-induced production of LT and was a more potent inhibitor of histamine release (IC50 = 13.4 microM) than proxicromil (IC50 = 72.9 microM), or cromolyn (inactive at 1 mM). CI-922 (IC50 = 0.9 microM) completely inhibited repeated contractions of guinea pig lung strips that were induced by low antigen concentration in the presence of antihistamine (H1). Nordihydroguaiaretic acid (NDGA) (IC50 = 2.8 microM), proxicromil (IC50 = 6.2 microM) and the LT antagonist FPL-55712 (IC50 = 3.3 microM) also were fully effective, but cromolyn (300 microM) was inactive. In other experiments, CI-922 (IC50 = 7.0 microM) inhibited a strong, nonrepeatable lung contraction induced with high antigen concentration (histamine responses blocked), and was six times more potent than FPL-55712. Other investigations in isolated tissue preparations showed CI-922 to be a weak inhibitor of LT or histamine-induced effects with no anticholinergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011863:Radioimmunoassay; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D001393:Azoles; D007211:Indoles; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; D013777:Tetrazoles; C045584:CI 922; D002217:Carbachol