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.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan. satoh_k@yamanouchi.co.jp
K
K
Sato
T
T
Kawasaki
N
N
Hisamichi
Y
Y
Taniuchi
F
F
Hirayama
H
H
Koshio
M
M
Ichihara
Y
Y
Matsumoto
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