Inhibitory effect of DS-4574, a new potent leukotriene antagonist, on the release of mediators from rat peritoneal cells

• Published in: Japanese Journal of Pharmacology 1989, Vol.49 (suppl), p.163-163
• Main Authors: Iwamoto, Teiji, Aibara, Shunzo, Mori, Mikio, Takata, Yoshimi, Tsukada, Wataru
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)56333-8

DS-4574 is a potent leukotriene antagonist and has been shown to be effective in various experimental models of allergic asthma. We have examined the effects of this compound on 48-hr homologous passive cutaneous anaphylaxis (PCA) in rats and histamine release from rat peritoneal cells in vivo and in vitro. DS-4574 (from 0.3 to 10 mg/kg orally) significantly inhibited PCA in a dose-dependent manner. DS-4574(from 3 to 10 mg/kg orally) reduced the release of histamine and slow reacting substance of anaphylaxis (SRS-A) in passive peritoneal anaphylaxis. DS-4574 inhibited histamine release from peritoneal exudate cells induced by antigen, anti-IgE and concanavalin A at 10-7 to 10-5 M, but showed only slight effects on the response induced by compound 48/80, Ca ionophore A23187 and substance P. On the other hand, disodium cromoglycate (DSCG) inhibited histamine release stimulated by all of the above agents except for A23187. This mode of action seems to be different from that of DSCG. These findings suggest that DS-4574, in addition to leukotriene antagonistic activity, has inhibitory activity on histamine release from peritoneal cells.