Mechanism of inhibition of tumor necrosis factor production by chlorpromazine and its derivatives in mice.
Eur J Pharmacol
; 317(2-3): 369-76, 1996 Dec 19.
Article
en En
| MEDLINE
| ID: mdl-8997623
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 A2, 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 A2 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Clorpromazina
/
Factor de Necrosis Tumoral alfa
/
Antioxidantes
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
1996
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos