Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumorostatic agent.

Abstract	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-1beta 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.
Authors	Lei Guo, Caiying Ye, Wenying Chen, Hua Ye, Ru Zheng, Juan Li, Huifen Yang, Xiaoli Yu, Dechang Zhang
Journal	The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 325 Issue 1 Pg. 10-6 (Apr 2008) ISSN: 1521-0103 [Electronic] United States
PMID	18182559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Analgesics Anti-Inflammatory Agents Antineoplastic Agents Interleukin-1 Triazoles Tumor Necrosis Factor-alpha carboxyamido-triazole
Topics	Analgesics (pharmacology) Animals Anti-Inflammatory Agents (pharmacology) Antineoplastic Agents (therapeutic use) Arthritis (drug therapy) Capillary Permeability (drug effects) Disease Models, Animal Edema (drug therapy) Female Granuloma (drug therapy) Interleukin-1 (antagonists & inhibitors) Male Mice Mice, Inbred ICR Pain (drug therapy) Pain Measurement Rats Rats, Wistar Triazoles (pharmacology, therapeutic use) Tumor Necrosis Factor-alpha (drug effects)

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