Effect of AS-35 on Agonist-Induced Contractions and the Resting Tonus of Airway Smooth Muscles and the In Vitro Release of Chemical Mediators from Passively Sensitized Lung Fragments from Humans and Guinea Pigs.

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Effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido [1, 2-a]pyrimidin-4-one (AS-35) on the resting tonus or contractions induced by agonists, such as leukotriene (LT) D4 and specific antigen of isolated guinea pig tracheas or human bronchi, and the in vitro anaphylactic release of histamine and LTs from human lung fragments were investigated and compared with the effects of FPL 55712 and disodium cromoglycate. AS-35 as well as FPL 55712 did not affect the contractions induced by acetylcholine and histamine of the isolated guinea pig trachea. However, the compound at relatively low concentrations obviously inhibited contractions induced by LTD4, and the antagonistic activity was stronger than that of FPL 55712. Treatment of the isolated human bronchus with AS-35 tended to induce the inhibition of both LTD4- and antigen-induced contractions and the relaxation of the resting tonus in a concentration-dependent manner. The inhibitory potency at 10-6 g/ml was slightly stronger than that of FPL 55712, but this was not statistically significant. The anaphylactic release of histamine and LTs from the lung fragments appeared to be inhibited by the treatment with AS-35 5 min prior to the antigen challenge. From these results, it is suggested that AS-35 is effective against allergic asthma through antagonism towards peptide-LTs released anaphylactically in addition to inhibition of the chemical mediator release.
公益社団法人日本薬理学会の論文

Effect of AS-35 on Agonist-Induced Contractions and the Resting Tonus of Airway Smooth Muscles and the In Vitro Release of Chemical Mediators from Passively Sensitized Lung Fragments from Humans and Guinea Pigs.

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