Inhibitory effect of DS-4574 on leukotriene- or antigen-induced bronchoconstriction in guinea pigs.
We studied the leukotriene (LT) antagonistic activity of DS-4574 in vivo and the inhibitory effect of this compound on antigen-induced bronchoconstriction in actively sensitized guinea pigs. Bronchoconstriction induced by LTD4 was inhibited by intravenous and oral treatment with DS-4574 in a dose-dependent manner. Orally administered DS-4574 was also able to inhibit the bronchoconstriction mediated by intravenous administration of LTC4 and E4 and that by endogenous LTs. The inhibitory effect of DS-4574 showed similar potency to those of FPL-55712 and LY171883. In contrast, histamine-, acetylcholine- or 5-hydroxytryptamine-induced bronchoconstriction was not significantly affected by DS-4574. Moreover, DS-4574 given orally or intravenously inhibited antigen-induced bronchoconstriction in actively sensitized guinea pigs and this compound prevented antigen-induced mediator release from actively sensitized guinea-pig lung fragments. The anti-asthmatic effect of this compound appears to be associated with LT antagonism and inhibition of the release of chemical mediators. This study therefore shows DS-4574 to have orally effective LT antagonistic and anti-asthmatic activities. This compound may prove useful in the treatment of bronchial asthma.
Aibara
S
S
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.
Mori
M
M
Tsukada
W
W
D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D017999:Leukotriene E4; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology*
D000941:Antigens; D020024:Leukotriene Antagonists; D011743:Pyrimidines; D013189:SRS-A; D014230:Triazoles; C076052:DS 4574; D017999:Leukotriene E4; D001285:Atropine; D011738:Pyrilamine; D007213:Indomethacin