Newly discovered anti-inflammatory properties of the benzamides and nicotinamides

Our laboratory has concentrated on the possible regulation the benzamides and nicotinamides may have on the processes of DNA repair and apoptosis. Recent reports have suggested that both apoptosis and inflammation are regulated by the transcription factor NF-kappaB. We have initiated studies regardi...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 1999-03, Vol.193 (1-2), p.119
Main Authors: Pero, R W, Axelsson, B, Siemann, D, Chaplin, D, Dougherty, G
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Apoptosis
Benzamides - chemistry
Benzamides - pharmacology
Cytokines - antagonists & inhibitors
Disease Models, Animal
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Edema
Edema - drug therapy
HeLa Cells
Humans
Mice
Mice, Inbred CBA
Models, Biological
NF-kappa B - antagonists & inhibitors
Niacinamide - analogs & derivatives
Niacinamide - chemistry
Niacinamide - pharmacology
Proteins
Rats
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary:Our laboratory has concentrated on the possible regulation the benzamides and nicotinamides may have on the processes of DNA repair and apoptosis. Recent reports have suggested that both apoptosis and inflammation are regulated by the transcription factor NF-kappaB. We have initiated studies regarding the hypothesis that the benzamides and nicotinamides could inhibit the production of tumor necrosis factor alpha (TNFalpha) and the inflammatory response as well as induce apoptosis via inhibition of NF-kappaB. Our data have shown that nicotinamide and two N-substituted benzamides, metoclopramide (MCA) and 3-chloroprocainamide (3-CPA), gave dose dependent inhibition of lipopolysacharide induced TNFalpha in the mouse within the dose range of 10-500 mg/kg. Moreover, lung edema was prevented in the rat by 3 x 50 mg/kg doses of 3-CPA or MCA, and 100-200 microM doses of MCA could also inhibit NF-kappaB in Hela cells. Taken together these data strongly support the notion that benzamides and nicotinamides have potent anti-inflammatory and antitumor properties, because their primary mechanism of action is regulated by inhibition at the gene transcription level of NF-kappaB, which in turn inhibits TNFalpha and induces apoptosis.
ISSN:0300-8177
1573-4919
DOI:10.1023/A:1006932714982