CI-922--a novel, potent antiallergic compound--II. Activity in animal models of allergy

CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo [3,2-b]indole-2-carboxamide, L-arginine salt) is an effective antiallergic in guinea pig, rat, and canine models. This in vivo activity is attributed to its ability to inhibit inflammatory mediator release following antigen challenge in these species. Antigen-induced anaphylaxis in guinea pigs (collapse), which is mediated predominantly by histamine, was prevented by i.p. drug pretreatment. CI-922 (5 mg/kg, i.v.) reduced i.v. antigen-induced falls in pulmonary compliance in mepyramine-pretreated, anesthetized guinea pigs. By comparison, cromolyn sodium was inactive in both guinea pig models. In rats, CI-922 given immediately before antigen challenge (ID50 of 0.29 mg/kg, i.v.) was effective and twice as potent as cromolyn sodium and twenty times more potent than proxicromil in preventing i.v. antigen-induced pulmonary anaphylaxis. In addition, when the drugs were given 10 min before antigen challenge, only CI-922 caused a dose-related reduction of bronchoconstriction. CI-922 did not show direct antagonist activity when tested against a serotonin-induced bronchospasm, and exhibited only slight activity against a histamine-induced bronchospasm. CI-922 (0.3 mg/kg, i.v.) also...Continue Reading