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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on January 8, 2008; DOI: 10.1124/jpet.107.131888

0022-3565/08/3251-10-16$20.00
JPET 325:10-16, 2008
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INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Anti-Inflammatory and Analgesic Potency of Carboxyamidotriazole, a Tumorostatic Agent

Lei Guo, Caiying Ye, Wenying Chen, Hua Ye, Ru Zheng, Juan Li, Huifen Yang, Xiaoli Yu, and Dechang Zhang

Department of Pharmacology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China

Carboxyamidotriazole (CAI) is a calcium influx inhibitor that is undergoing clinical trials for the treatment of various human cancers following the identification of its antiproliferative and antimetastatic activities. The exact mechanism of its action is not clearly understood, and whether it has other functions besides the established antitumor activity has not been reported either. In the present study, we demonstrate for the first time that CAI possesses anti-inflammatory and analgesic activities using a variety of animal models, including croton oil-induced ear edema, cotton-induced granuloma, rat adjuvant-induced arthritis, acetic acid-induced writhing, and the formalin test. We also show that CAI significantly inhibits local vascular permeability stimulated by vascular endothelial growth factor or histamine and decreases tumor necrosis factor-{alpha} and interleukin-1β levels at the site of inflammation and in serums, which may contribute to the anti-inflammatory effect. These data suggest that CAI is a promising anti-inflammatory and analgesic agent, and they provide new insight into the biological activity of the drug.

Received September 19, 2007; accepted January 7, 2008.

Address correspondence to: Dr. Dechang Zhang, Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, No. 5 Santiao, Dongdan, Beijing 100005, China. E-mail: pumc01{at}126.com






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