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

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Author(s)

    • Ohga Keiko OHGA Keiko
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • Suwa Kiyomi [他] SUWA Kiyomi
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • OKADA Yohei
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • MORIO Hiroki
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • YOKOTA Masaki
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • MIYATA Keiji
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • YAMADA Toshimitsu
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
    • HONDA Kazuo
    • Inflammation Research Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

Abstract

The effects of lipid mediator antagonists:the LTD<SUB>4</SUB>-receptor antagonist pranlukast, the TXA<SUB>2</SUB>-receptor antagonist seratrodast, and the novel dual LTD<SUB>4</SUB>- and TXA<SUB>2</SUB>-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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 82(4), 287-294, 2000-04-01

    The Japanese Pharmacological Society

References:  31

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008183771
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5362696
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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