Pharmacological studies on the novel antiallergic drug HQL-79: II. Elucidation of mechanisms for antiallergic and antiasthmatic effects

被引：43

作者：

Matsushita, N ^{[1
]}

Aritake, K ^{[1
]}

Takada, A ^{[1
]}

Hizue, M ^{[1
]}

Hayashi, K ^{[1
]}

Mitsui, K ^{[1
]}

Hayashi, M ^{[1
]}

Hirotsu, I ^{[1
]}

Kimura, Y ^{[1
]}

Tani, T ^{[1
]}

Nakajima, H ^{[1
]}

机构：

[1] Sumitomo Met Ind Ltd, Div Biomed, High Qual Life Res Labs, New Drug Res Dept, Kyoto 6190237, Japan

来源：

JAPANESE JOURNAL OF PHARMACOLOGY | 1998年 / 78卷 / 01期

关键词：

antihistamine; prostaglandin D-2; prostaglandin E-2; prostaglandin D synthase; HQL-79;

D O I：

10.1254/jjp.78.11

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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) B-4, LTC4, histamine and prostaglandin (PG)D-2 from the chopped lung tissues of actively sensitized guinea pigs. On the other hand, release of PGE(2), one of the bronchoprotective prostanoids, was significantly enhanced by HQL-79. In an in vivo experiment, chronic administration of HQL-79 clearly reduced PGD(2) contents and enhanced PGE(2) 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-MT effects, chemical mediator release inhibition, PGE(2)-release enhancement and PGD synthase inhibition. It is considered, in particular, that the differential modulation of PGD(2) and PGE(2) production is a conspicuous pharmacological feature of HQL-79.

引用

页码：11 / 22

页数：12

共 32 条

[1] EFFECTS OF ZCR-2060 ON ALLERGIC AIRWAY INFLAMMATION AND CELL ACTIVATION IN GUINEA-PIGS [J].