Antithrombotic effects of YM-60828 in three thrombosis models in guinea pigs

• Published in: European journal of pharmacology Vol. 350; no. 1; pp. 87 - 91
• Main Authors: Sato, Kazuo, Kawasaki, Tomihisa, Hisamichi, Nami, Taniuchi, Yuta, Hirayama, Fukushi, Koshio, Hiroyuki, Ichihara, Masato, Matsumoto, Yuzo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29.05.1998; Elsevier
• Subjects: Animals; Antithrombin III - pharmacology; Antithrombin III - therapeutic use; Arterial thrombosis; Arteriovenous Shunt, Surgical; Biological and medical sciences; Bleeding Time; Blood. Blood coagulation. Reticuloendothelial system; Carotid Artery Thrombosis - drug therapy; Carotid Artery Thrombosis - metabolism; Carotid Artery, Internal - drug effects; Disease Models, Animal; Factor Xa inhibitor; Factor Xa Inhibitors; Fibrinolytic Agents - therapeutic use; Guinea Pigs; Male; Medical sciences; Naphthalenes - pharmacology; Naphthalenes - therapeutic use; Pharmacology. Drug treatments; Piperidines - pharmacology; Piperidines - therapeutic use; Thrombophlebitis - drug therapy; Thrombophlebitis - metabolism; Thrombosis - drug therapy; Venous thrombosis; YM-60828; Arterial thrombosis; YM-60828; Venous thrombosis; Bleeding time; Factor Xa inhibitor; Intravenous administration; Serine endopeptidases; Enzyme; Rodentia; Cardiovascular disease; Coagulation Factor Xa; Anticoagulant; Thrombosis; Biological activity; Artery; Venous disease; Arterial disease; Vascular disease; Peptidases; Vertebrata; Mammalia; Guinea pig; Animal; Hydrolases; Inhibitor; Vein
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00328-8

The antithrombotic effects of a novel factor Xa inhibitor, YM-60828 ([ N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]- N-[(7-amidino-2-naphthyl)methyl]sulfamoyl]acetic acid dihydrochloride), in three thrombosis models in guinea pigs were studied in comparison with its effect on bleeding time. The antithrombotic effects of YM-60828 were most pronounced in the venous thrombosis and the arterio-venous shunt models but YM-60828 showed 10-fold weaker effects in the carotid thrombosis model. However, YM-60828 prolonged bleeding time at a much higher dose than that required in all thrombosis models. In conclusion, YM-60828 exerted its antithrombotic effects without prolonging bleeding time in all thrombosis models and may be of clinical value not only in venous thrombosis but also in arterial thrombosis.