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

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Author(s)

    • Aritake Kosuke ARITAKE Kosuke
    • New Drug Research Department, High Quality-Life Research Laboratories, Bio-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.

Abstract

The effects of 4-benzhydryloxy-1-{3-(1<I>H</I>-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) B<SUB>4</SUB>, LTC<SUB>4</SUB>, histamine and prostaglandin (PG) D<SUB>2</SUB> from the chopped lung tissues of actively sensitized guinea pigs. On the other hand, release of PGE<SUB>2</SUB>, one of the bronchoprotective prostanoids, was significantly enhanced by HQL-79. In an in vivo experiment, chronic administration of HQL-79 clearly reduced PGD<SUB>2</SUB> contents and enhanced PGE<SUB>2</SUB> 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, PGE<SUB>2</SUB>-release enhancement and PGD synthase inhibition. It is considered, in particular, that the differential modulation of PGD<SUB>2</SUB> and PGE<SUB>2</SUB> production is a conspicuous pharmacological feature of HQL-79.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(1), 11-22, 1998-09

    The Japanese Pharmacological Society

References:  32

Cited by:  3

Codes

  • NII Article ID (NAID)
    10008193568
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4565698
  • 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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