Mechanism of inhibition of tumor necrosis factor production by chlorpromazine and its derivatives in mice

被引：17

作者：

Ghezzi, P ^{[1
]}

Garattini, S ^{[1
]}

Mennini, T ^{[1
]}

Bertini, R ^{[1
]}

Hernandez, RD ^{[1
]}

Benigni, F ^{[1
]}

Sacco, S ^{[1
]}

Skorupska, M ^{[1
]}

Mengozzi, M ^{[1
]}

Latini, R ^{[1
]}

Kurosaki, M ^{[1
]}

Lombet, A ^{[1
]}

Fradin, A ^{[1
]}

Bonnet, J ^{[1
]}

Rolland, Y ^{[1
]}

Brion, JD ^{[1
]}

机构：

[1] INST RECH SERVIER, SURESNES, FRANCE

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1996年 / 317卷 / 2-3期

关键词：

chlorpromazine; TNF (tumor necrosis factor); endotoxin;

D O I：

10.1016/S0014-2999(96)00728-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In previous work, we reported that chlorpromazine inhibits tumor necrosis factor (TNF) production in endotoxin lipopolysaccharide-treated mice, and protects against lipopolysaccharide toxicity. Chlorpromazine is used as an antipsychotic and has several effects on the central nervous system. It acts on different neurotransmitter receptors and has other biochemical activities some of which, like inhibition of phospholipase A(2), might be responsible for the inhibitory effect on TNF production. To investigate the role of these actions in the inhibition of TNF production by chlorpromazine, we have synthesized some chlorpromazine derivatives that do not have central activities. Some of these analogs have lost their affinity for various receptors and their phospholipase A(2) inhibitory activity, but still inhibit TNF production. No correlation was found between TNF inhibition and the ability to inhibit nitric oxide (NO) synthase, whereas a good correlation was evident between TNF inhibition and antioxidant activity.

引用

页码：369 / 376

页数：8

共 26 条

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