Antithrombotic effect of YM-75466 is separated from its effect on bleeding time and coagulation time

• Published in: European journal of pharmacology Vol. 352; no. 1; pp. 59 - 63
• Main Authors: Sato, Kazuo, Kaku, Seiji, Hirayama, Fukushi, Koshio, Hiroyuki, Matsumoto, Yuzo, Kawasaki, Tomihisa, Iizumi, Yuichi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.07.1998; Elsevier
• Subjects: Animals; Anticoagulants - pharmacology; Biological and medical sciences; Bleeding Time; Blood Coagulation - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Factor Xa inhibitor; Fibrinolytic Agents - pharmacology; Male; Medical sciences; Oral anticoagulant; Pharmacology. Drug treatments; Piperidines - pharmacology; Rats; Rats, Sprague-Dawley; Sulfonamides - pharmacology; Thromboplastin - pharmacology; Venous thrombosis; Warfarin; Warfarin - pharmacology; YM-75466; Warfarin; Venous thrombosis; Bleeding time; Oral anticoagulant; Factor Xa inhibitor; YM-75466; Serine endopeptidases; Rat; Enzyme; Coumarine derivatives; Rodentia; Coagulation; Oral administration; Cardiovascular disease; Coagulation Factor Xa; Anticoagulant; Thrombosis; Biological activity; Antiplatelet agent; Venous disease; Vascular disease; Peptidases; Vertebrata; Mammalia; Animal; Hydrolases; Vein
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00339-2

The antithrombotic effects of YM-75466 ([ N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]- N-[(7-amidino-2-naphthyl)methyl]sulfamoyl]acetic acid monomethane sulfonate), a novel orally-active factor Xa inhibitor, and its effects on bleeding time and coagulation time were studied in rats and compared with those of warfarin. Both agents were orally administered. In the venous thrombosis model, YM-75466 and warfarin inhibited thrombus formation dose-dependently, with ID 50 values of 3.3 and 0.56 mg/kg, respectively. Ex vivo study showed that both YM-75466 and warfarin prolonged prothrombin time dose-dependently, with doses, causing a two-fold prolongation of prothrombin time in the control group, of 89 and 0.38 mg/kg, respectively. In bleeding time studies, YM-75466 and warfarin prolonged bleeding time dose-dependently, with doses, causing a two-fold prolongation of bleeding time in the control group, of >100 and 0.43 mg/kg, respectively. These results show that the antithrombotic effects of YM-75466 are markedly separate from its effects on bleeding time and coagulation time compared with warfarin.