EFFECTS OF PYRIDINYL IMIDAZOLE COMPOUNDS ON MURINE TNF-ALPHA PRODUCTION

被引：10

作者：

OLIVERA, DL ^{[1
]}

LAYDON, JT ^{[1
]}

HILLEGASS, L ^{[1
]}

BADGER, AM ^{[1
]}

LEE, JC ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT PHARMACOL,KING OF PRUSSIA,PA 19406

来源：

AGENTS AND ACTIONS | 1993年 / 39卷

关键词：

D O I：

10.1007/BF01972719

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The effects of SK&F 86002 and other pyridinyl imidazole compounds on murine cytokine production were investigated. In vitro, SK&F 86002 inhibited LPS stimulated TNF-alpha production by the RAW 264.7 cell line and by oil elicited peritoneal macrophages with an IC50 of 5 muM. In general, the activity was reflective of previous results obtained with human monocytes as SK&F 86002 and its analogs demonstrated identical rank order potency for TNF-alpha inhibition in both species. These compounds also inhibited TNF-alpha in vivo in a murine model of endotoxin shock. Following oral administration, SK&F 86002 and its analogs reduced serum TNF-alpha levels by > 80% and afforded 100% protection from lethality. In contrast, tenidap, a novel anti-inflammatory drug, had minimal to no effect on murine TNF-alpha production in the same assays. These data further extend the pharmacological profile of the pyridinyl imidazoles by demonstrating that these compounds potently inhibit murine TNF-alpha production both in vitro and in vivo.

引用

页码：C55 / C57

页数：3

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