Effect of AA 673, a new anti-allergic agent on experimental asthma

The effects of a new anti-allergic agent, 2-amino-7-isopropyl-5-oxo-5H-[l]benzopyrano[2,3-b]pyridine-3-carboxylic acid (AA 673) on various models of asthma were investigated in Hartley guinea pigs (G. pigs) and SD rats. The experimental allergic asthma was induced by i.v. administration or inhalation of egg albumin (EA) in G. pigs and rats sensitized actively with EA and alum or killed B. pertussis (IgE-mediated asthma), and in G. pigs sensitized actively with EA and Freund1 s complete adjuvant or passively with rabbit anti-EA antiserum (IgG-medi-ated asthma). The bronchoconstrictions elicited by chemical mediators in G. pigs were examined using leukotriene D4 (LTD4, 10 μg/kg), platelet activating factor (PAF, 0.3 μg/kg), histamine (His, 10 μg/kg), and acetylcholine (ACh, 30 μg/kg). The immunologically- and chemical mediator-induced bronchoconstrictions were measured by the method of Konzett-Rossler. AA 673 suppressed the IgE- and IgG-mediated asthma in a dose-related manner by either i.v. or p.o. Its inhibitory doses were 2.5-10 mg/kg, i.V., or 100-300 mg/kg, p.o.,in G. pigs and 0.1-1 mg/kg, i.v.,or 1-10 mg/kg, p.o.,in rats. AA 673 inhibited the LTD4- and PAF-induced bronchoconstrictions at doses of 5-20 mg/kg, i.V.; it moderately reduced that induced by His, but not that induced by ACh. In conclusion, AA 673 is expected to be effective on human bronchial asthma.