[Effect of AS-35 aerosol on bronchoconstriction induced by specific antigens in macacus rhesus monkeys].
In a previous in vitro study, 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H- pyrido[1,2-a]pyrimidin-4-one (AS-35) was shown to have an inhibitory effect on antigen-induced mediator release and an antagonistic effect on leukotriene C4 and D4 receptors. In the present study, therefore, we investigated the effect of AS-35 aerosol on allergen-induced bronchoconstriction, using 6 female Macacus rhesus monkeys sensitized with DNP-Ascaris extracts (DNP-As). After treatment with an inactive placebo, inhalation challenge with DNP-As increased total lung resistance and decreased dynamic lung compliance dose-dependently 1 week after sensitization with DNP-As. Treatment with AS-35 aerosol, however, significantly inhibited allergen-induced bronchoconstriction dose-dependently 2 weeks after the sensitization. The inhibitory effect was about ten times more potent than that of DSCG. Because we confirmed that DNP-As evoked almost the same bronchoconstriction 1 and 2 weeks after sensitization and also that AS-35 did not inhibit histamine-induced bronchoconstriction at all, we inferred that AS-35 diminished allergen-induced bronchoconstriction by inhibiting allergen-induced mediator release from the cells in the airway.
Takata
H
H
First Department of Internal Medicine, Tohoku University School of Medicine.
Tamura
G
G
Shibasaki
A
A
Honma
M
M
Takishima
T
T
D000336:Aerosols; D000485:Allergens / Q000276:immunology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D008253:Macaca mulatta; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology*; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*
D000336:Aerosols; D000485:Allergens; D001993:Bronchodilator Agents; D011725:Pyridines; D011744:Pyrimidinones; D013777:Tetrazoles; C073308:AS 35