Therapeutic Potential of a Specific Chymase Inhibitor in Atopic Dermatitis

DOI Web Site Web Site Web Site PubMed 被引用文献4件 参考文献27件 オープンアクセス

書誌事項

タイトル別名
  • Development and Application of Chymase Inhibitors. Therapeutic Potential of a Specific Chymase Inhibitor in Atopic Dermatitis.

この論文をさがす

説明

A novel therapeutic mechanism may be the key to improving the chief symptoms and signs of atopic dermatitis (AD), which are persistent pruritus and high serum IgE. We demonstrate here that mast cell chymase may be a possible initiating factor and that the orally active specific inhibitor Y-40613 may have a therapeutic potential in the treatment of AD. We found that Y-40613 (2-[5-amino-2-(4-fluorophenyl)-1,6-dihydro-6-oxo-1-pyrimidinyl]-N-{1-[(5-methoxycarbonyl-2-benzoxazolyl)carbonyl]-2-phenylethyl}acetamide) dose-dependently suppressed the scratching response in a mouse pruritus model, with inhibitory efficacy enhanced by combination with conventional drugs, suggesting that chymase contributes to the development of pruritus by a unique mechanism or mechanisms. In fact, chymase injected in the model induced the scratching response. In vitro IgE production from mouse B cells was increased by purified rat chymase and suppressed by Y-40613. Increased serum IgE observed in Brown Norway rats injected with mercury chloride was suppressed by Y-40613. Furthermore, Y-40613 lowered ear thickness as well as serum IgE level in a mouse contact dermatitis model. Taken together, these findings suggest that the specific chymase inhibitor Y-40613 may ameliorate symptoms of AD through the dual inhibition of the chymase-dependent IgE production pathway and itching sensation.<br>

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 90 (3), 214-217, 2002

    公益社団法人 日本薬理学会

被引用文献 (4)*注記

もっと見る

参考文献 (27)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ