Pharmacological Studies on the Novel Antiallergic Drug HQL-79: 2. Elucidation of Mechanisms for Antiallergic and Antiathmatic Effects

• Matsushita Nobutoshi

  Present address for correspondence: Pharmacological Research Group, Bioclinical Research Division, Rohto Pharmaceutical Co., Ltd.

• Aritake Kosuke

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Takada Ayumi

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Hizue Masanori

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Hayashi Kumi

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Mitsui Kazuhiko

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Hayashi Masatoshi

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Hirotsu Ichiro

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Kimura Yoshiyuki

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Tani Tadato

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

• Nakajima Hiromichi

  New Drug Research Department, High Quality-Life Research Laboratories, Bio-Medical Division, Sumitomo Metal Industries, Ltd.

書誌事項

タイトル別名

• Pharmacological Studies on the Novel Antiallergic Drug HQL-79:II. Elucidation of Mechanisms for Antiallergic and Antiasthmatic Effects.
• Pharmacological Studies on the Novel An

抄録

The effects of 4-benzhydryloxy-1-{3-(1H-tetrazol-5-yl)-propyl}piperidine (HQL-79), a newly developed antiallergic drug, on various chemical mediators and on chemical mediator release were investigated. Orally administered HQL-79 strongly inhibited the histamine-induced skin reaction in rats, and histamine- and 5-hydroxytryptamine (5-HT)-induced bronchoconstriction in guinea pigs. HQL-79 inhibited antigen-induced release of leukotriene (LT) B₄, LTC₄, histamine and prostaglandin (PG) D₂ from the chopped lung tissues of actively sensitized guinea pigs. On the other hand, release of PGE₂, one of the bronchoprotective prostanoids, was significantly enhanced by HQL-79. In an in vivo experiment, chronic administration of HQL-79 clearly reduced PGD₂ contents and enhanced PGE₂ contents in the lungs of repeatedly antigen-exposed guinea pigs. In biochemical studies, HQL-79 inhibited mouse spleen PGD synthase in a concentration-dependent manner. None of the antiallergics such as epinastine, terfenadine, oxatomide and cetirizine inhibited the PGD synthase. HQL-79 did not affect PGE synthase in sheep vesicular gland microsomes. These results suggest that antiallergic and antiasthmatic effects of HQL-79 could be ascribed to antihistaminic- and anti-5-HT effects, chemical mediator release inhibition, PGE₂-release enhancement and PGD synthase inhibition. It is considered, in particular, that the differential modulation of PGD₂ and PGE₂ production is a conspicuous pharmacological feature of HQL-79.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 78 (1), 11-22, 1998

  公益社団法人 日本薬理学会

キーワード

• Antihistamine
• Prostaglandin D<SUB>2</SUB>
• Prostaglandin E<SUB>2</SUB>
• Prostaglandin D synthase
• HQL-79

詳細情報

• CRID: 1390282679263523456
• NII論文ID: 10008193568
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.78.11
• COI: 1:CAS:528:DyaK1cXmtlCktb0%3D
• ISSN: 13473506
• ISSN: 00215198
• ISSN: http://id.crossref.org/issn/00215198
• NDL書誌ID: 4565698
• PubMed: 9804057
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4565698
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819310637?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819310637?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/78/1/78_1_11/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1999001061
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可