title: 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.affiliation: Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, No. 5 Santiao, Dongdan, Beijing 100005, China. pumc01@126.com
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Caiying
authors.initials: C
authors.lastname: Ye
authors.forename: Wenying
authors.initials: W
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
authors.forename: Ru
authors.initials: R
authors.lastname: Zheng
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Huifen
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yu
authors.forename: Dechang
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D005260:Female; D006099:Granuloma / Q000188:drug therapy; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D007375:Interleukin-1; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C062058:carboxyamido-triazole