INHIBITION OF LEUKOTRIENE BIOSYNTHESIS IN THE RAT PERITONEAL-CAVITY

被引：24

作者：

YOUNG, PR

BELL, RL

LANNI, C

SUMMERS, JB

BROOKS, DW

CARTER, GW

机构：

[1] Immunosciences Research Area, Abbott Laboratories, Abbott Park

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1991年 / 205卷 / 03期

关键词：

LEUKOTRIENE BIOSYNTHESIS; 5-LIPOXYGENASE INHIBITION; ZILEUTON; PERITONEAL ANAPHYLAXIS MODEL (RAT); (INVIVO ACTIVITY);

D O I：

10.1016/0014-2999(91)90907-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In the search for a model of leukotriene (LT) production to provide a method to determine in vivo 5-lipoxygenase (5-LO) inhibitory activity by various compounds, a passive anaphylactic reaction in the rat peritoneal cavity was examined, refined and characterized. The reaction, produced by passive sensitization with an i.p. injection of rabbit anti-bovine serum albumin (anti-BSA) followed by an i.p. injection of BSA, resulted in the biosynthesis of large amounts of sulfidopeptide LTs measurable by immunoassay or by reversed phase high performance liquid chromatography. The oral activity of several 5-LO inhibitors has been examined using this model. An example of these is zileuton (Abbott-64077), a potent 5-lipoxygenase inhibitor now under clinical evaluation. Zileuton inhibited sulfidopeptide LT biosynthesis in the rat peritoneal cavity in a dose-dependent manner (ED50 = 3 mg/kg). WY-49,232, MK-866, BW A4C and phenidone also produced good activity with ED50 values of 6, 8, 11 and 17 mg/kg, respectively. This modified rat peritoneal anaphylaxis model appears to be a valuable tool for establishing in vivo activity of 5-LO inhibitors.

引用

页码：259 / 266

页数：8

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