In Vivo Pharmacologic Profile of YM158, a New Dual Antagonist for Leukotriene D_4 and Thromboxane A_2 Receptors

この論文にアクセスする

この論文をさがす

著者

    • Ohga Keiko OHGA Keiko
    • 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

抄録

The antagonistic activity of oral YM158(3−[(4−tert−butylthiazol−2−yl)methoxy]−5′−[3−(4−chlorobenzenesulfonyl)propyl]−2′−(1H−tetrazol−5−ylmethoxy)benzanilide monosodium salt monohydrate), a new dual antagonist for leukotriene(LT)D<SUB>4</SUB> and thromboxane(TX)A<SUB>2</SUB> receptors, was investigated.Oral YM158 caused dose−dependent inhibition of LTD<SUB>4</SUB>−induced increases in plasma leakage and LTD<SUB>4</SUB>− or U46619−induced increases in airway resistance, with ED<SUB>5</SUB>0 values of 6.6, 8.6 and 14 mg/kg, respectively.The dose−range of YM158's inhibitions was almost the same for both LTD<SUB>4</SUB> and TXA<SUB>2</SUB> receptors, and repeated oral doses did not affect its efficacy.Furthermore, oral YM158 inhibited antigen−induced bronchoconstriction.Although the potency of pranlukast for LTD<SUB>4</SUB> receptor antagonism(ED<SUB>5</SUB>0=0.34 mg/kg)is greater than that of YM158(ED<SUB>5</SUB>0=8.6 mg/kg), the doses of both pranlukast and YM158 for significant inhibition of the antigen−evoked airway response were the same, indicating that the TXA<SUB>2</SUB> receptor antagonism of YM158 plays an important role in its anti−asthmatic effects.In conclusion, YM158 promises to be a novel agent for treating bronchial asthma.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 83(1), 63-72, 2000-05-01

    公益社団法人 日本薬理学会

参考文献:  38件中 1-38件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008184412
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5399718
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
ページトップへ