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

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.