Effect of YM158, a Dual Lipid Mediator Antagonist, on Immediate and Late Asthmatic Responses, and on Airway Hyper-responsiveness in Guinea Pigs

The Japanese Journal of Pharmacology

Keiji Miyata¹  Masaki Yokota¹  Yasuhito Arakida¹  Kiyomi Suwa¹  Kazuo Honda¹  Yohei Okada¹  Keiko Ohga¹  Toshimitsu Yamada¹  Hiroki Morio¹ 

[1] Inflammation Research Pharmacology Laboratories,Institute for Drug Discovery Research,Yamanouchi Pharmaceutical Co.,Ltd.,21 Miyukigaoka,Tsukuba-shi,Ibaraki 305-8585,Japan

关键词: YM158;    Leukotriene D4;    Thromboxane A2;    Receptor antagonist;    Asthma;   

DOI  :  10.1254/jjp.82.287

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(31)Cited-By(9)The effects of lipid mediator antagonists:the LTD4-receptor antagonist pranlukast, the TXA2-receptor antagonist seratrodast, and the novel dual LTD4- and TXA2-receptor antagonist YM158(3-[(4-tert-butylthiazol-2-yl)methoxy]-5′-[3-(4-chlorobenzenesulfonyl)propyl]-2′-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate)were investigated in animals exhibiting immediate asthmatic response(IAR), late asthmatic response(LAR)and airway hyper-responsiveness(AHR).Antigen-induced LAR and AHR are inhibited by orally administered pranlukast(30, 100mg/kg) and seratrodast(3, 10mg/kg).YM158(30mg/kg), orally administered before or after IAR induction, also inhibited both LAR and AHR.However, while the inhibitory effects of pranlukast and seratrodast on IAR were marginal, the effects of YM158(3, 10, 30mg/kg) were dose-dependent, probably due to its multiple sites of action.Additionally, orally administered YM158(30mg/kg) inhibited ozone-induced AHR in guinea pigs.Thus, an antagonist that inhibits several lipid mediators might exhibit greater efficacy in treating asthmatic responses than antagonists with a single site of action.Therefore, YM158 shows great promise as a drug that will be able to treat bronchial asthma and related disorders more potently than currently used single-pathway inhibitors.

【 授权许可】

Unknown