Abstract
A forced oscillations technique for measuring total respiratory system resistance was used to quantitate the bronchomotor activity of Sch 15280: (5[4-(N-methyl)-piperidylidine]5H-[1]-benzopyrano[2,3,b]-pyridine maleate) and to compare its potency to that of standard bronchodilator agents. By the intravenous route, Sch 15280 was 48 times more potent than aminophylline and 1/78 as potent as atropine in inhibiting methacholine-induced bronchoconstriction in rabbits. In cats Sch 15280 was 1/12 as potent as ephedrine in inhibiting histamine-induced bronchoconstriction and had a greater protective activity against histamine-induced bronchoconstriction and had a longer duration of action than 0.5% solution of isoproterenol. Statistical tests of parallelism revealed a significant difference between the log dose-response curves of Sch 15280 and ephedrine but not between those of Sch 15280, atropine and aminophylline. The results suggest that Sch 15280 can act via, a nonadrenergic mechanism to block both histaminergically and cholinergically mediated responses in the tracheobronchial tree. This pharmacologie profile may have important therapeutic application in the type I immediate hypersensitivity reactions of man.
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