Anti-thrombotic Activity of KBT-3022 in Experimental Models of Thrombosis

The Japanese Journal of Pharmacology

Koichi Yokota²  Akira Yamashita²  Minoru Oda¹ 

[1] Research Laboratories Torii Pharmaceutical Co., Ltd.;New Drug Research Laboratories, Kanebo, Ltd.

关键词: Anti-platelet agent;    KBT-3022;    Acetylsalicylic acid;    Ticlopidine;    Thrombosis model;   

DOI  :  10.1254/jjp.68.201

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(36)Cited-By(11)In this study, we investigated the effects of KBT-3022 (ethyl 2-[4, 5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate), a potent and long-lasting anti-platelet agent, in several experimental thrombosis models and compared them with those of other anti-platelet drugs. Oral administration of KBT-3022 prevented arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022, and ticlopidine hydrochloride (TP) showed no such effect in these models. In a guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus formation on a silk thread inserted into the shunt was dose-dependent and 300 and 30 times more potent than the inhibition obtained with ASA and indomethacin, respectively. In a model of aortic thrombosis induced by perivascular application of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had no effect. However, in a stasisinduced venous thrombosis model in guinea pigs, TP inhibited thrombus formation significantly, but KBT-3022 and ASA were ineffective. These results suggest that KBT-3022 may be a useful drug for the treatment and/or prophylaxis of thrombus formation in shunts and aortic thrombosis.

【 授权许可】

Unknown