Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumorostatic agent.
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.
Guo
Lei
L
Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, No. 5 Santiao, Dongdan, Beijing 100005, China. pumc01@126.com
Ye
Caiying
C
Chen
Wenying
W
Ye
Hua
H
Zheng
Ru
R
Li
Juan
J
Yang
Huifen
H
Yu
Xiaoli
X
Zhang
Dechang
D
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
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D007375:Interleukin-1; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C062058:carboxyamido-triazole