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-nap hthyl)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.
Sato
K
K
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan. satoh_k@yamanouchi.co.jp
Kawasaki
T
T
Hisamichi
N
N
Taniuchi
Y
Y
Hirayama
F
F
Koshio
H
H
Ichihara
M
M
Matsumoto
Y
Y
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology / Q000627:therapeutic use*; D001166:Arteriovenous Shunt, Surgical; D001760:Bleeding Time; D002341:Carotid Artery Thrombosis / Q000188:drug therapy / Q000378:metabolism; D002343:Carotid Artery, Internal / Q000187:drug effects; D004195:Disease Models, Animal; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D013924:Thrombophlebitis / Q000188:drug therapy / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy*
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D009281:Naphthalenes; D010880:Piperidines; C111032:YM 60828; D000990:Antithrombin III