Experimental study of a potential anti-asthmatic agent: SCH 15280.
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.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D000336:Aerosols; D001578:Benzopyrans; D001993:Bronchodilator Agents; D006634:Histamine H1 Antagonists; D008688:Methacholine Compounds; D010880:Piperidines; D011725:Pyridines; D000628:Aminophylline; C009983:azanator; D001285:Atropine; D007545:Isoproterenol