Pharmacologic studies on W10,294A, a new bronchodilator.
W10,294A (1,2,3,4-tetrahydro-8,9-dimethoxy-3(2-piperidinoethyl)-5H-[1] benzopyrano [3,4-c] pyridin-5-one dihydrochloride) is a potent antagonist of the bronchoconstriction induced by histamine, methacholine or acetylcholine. In vitro evaluation on guinea pig trachea indicated that W10,294A had both direct smooth muscle relaxant activity and modest antihistaminic properties. Resistance and dynamic compliance measurements in anesthetized dogs indicated that W10,294A prevented or reversed bronchoconstriction due to histamine or pilocapine. Bronchodilator activity of long duration was observed in dogs after oral administration. W10,294A was compared with aminophylline in several tests. W10,294A was 6 times more potent than aminophylline in relaxing isolated guinea-pig trachea. In the anesthetized dog W10,294A was more potent and longer acting than aminophylline in reversing pilocarpine-induced bronchospasm. The bronchodilator activity of W10,294A was not blocked by the beta adrenoceptor antagonist bunolol. Comparative studies in dogs and guinea pigs, using identical doses, showed that W10,294A had considerably less effect on the cardiovascular system than did aminophylline.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors; D001986:Bronchial Spasm / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010862:Pilocarpine / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology
D001993:Bronchodilator Agents; D003374:Coumarins; D006634:Histamine H1 Antagonists; D008688:Methacholine Compounds; D010880:Piperidines; D010862:Pilocarpine; D001464:Barium; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000109:Acetylcholine