Inhibitory effect of a novel phosphodiesterase IV inhibitor, T-440 on antigen-and chemical mediator-induced bronchoconstriction in guinea pigs (in vivo)

• Kaminuma Osamu

  <I>Lead</I> Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Kikkawa Hideo

  <I>Lead</I> Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Matsubara Shigeki

  <I>Lead</I> Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Ikezawa Katsuo

  <I>Lead</I> Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.

書誌事項

タイトル別名

• Inhibitory Effect of a Novel Phosphodiesterase IV Inhibitor, T-440, on Antigen- and Chemical Mediator-Induced Bronchoconstrictions in Guinea Pigs In Vivo.

抄録

We demonstrated the effect of a novel selective type IV phosphodiesterase (PDE) IV inhibitor, T-440 (1-[1-(2-methoxyethyl)pyrid-2-one-4-yl]-2, 3-bis(hydroxymethyl)-6, 7-diethoxynaphthalene), on antigen- and chemical mediator-induced bronchoconstrictions in anesthetized guinea pigs in vivo. Intravenously (i. v.) administered T-440 inhibited antigen-induced bronchoconstriction dose-dependently in passively sensitized guinea pigs (ED₅₀= 2.3 mg/kg). Histamine-, leukotriene (LT) D₄-, U-46619-, acetylcholine (ACh)-, neurokinin A- and endothelin-1-induced bronchoconstrictions were also inhibited by i. v. injected T-440. Most potent suppression was produced against the bronchoconstriction induced by LTD₄(ED₅₀= 0.89 μg/kg), whereas the effect against ACh was very weak (ED₅₀= 1.8 mg/kg). Additionally, T-440 inhibited histamine-induced bronchoconstriction by intraduodenal and intratracheal administration (ED₅₀and EC₅₀= 1.6mg/kg and 0.50mg/ml, respectively). Bronchoconstrictions induced by antigen and chemical mediators were also suppressed by theophylline. However, all of these anti-spasmolyiic effects of theophylline were less potent than those of T-440 (1.8-110times). Our results indicate the importance of PDE IV in bronchodilation, and PDE IV inhibitors may have potential as anti-asthma drugs.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 72 (1), 1-8, 1996

  公益社団法人 日本薬理学会

キーワード

• Phosphodiesterase
• Airway
• Asthma
• Bronchoconstriction

詳細情報

• CRID: 1390001204286344192
• NII論文ID: 10008675480
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.72.1
• COI: 1:CAS:528:DyaK28Xlsl2gurY%3D
• ISSN: 13473506
• ISSN: 00215198
• PubMed: 8902593
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819339393?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819339393?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/1997046495
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可