Sato K, Kaku S, Hirayama F, Koshio H, Matsumoto Y, Kawasaki T, Iizumi Y
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan.
Eur J Pharmacol. 1998 Jul 3;352(1):59-63. 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-nap hthyl)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 ID50 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.
新型口服活性Xa因子抑制剂YM-75466（[N-[4-[(1-脒基-4-哌啶基)氧基]苯基]-N-[(7-脒基-2-萘基)甲基]氨磺酰]乙酸甲磺酸盐）的抗血栓形成作用及其对大鼠出血时间和凝血时间的影响进行了研究，并与华法林进行了比较。两种药物均经口服给药。在静脉血栓形成模型中，YM-75466和华法林均剂量依赖性地抑制血栓形成，ID50值分别为3.3和0.56 mg/kg。体外研究表明，YM-75466和华法林均剂量依赖性地延长凝血酶原时间，在对照组中使凝血酶原时间延长两倍的剂量分别为89和0.38 mg/kg。在出血时间研究中，YM-75466和华法林均剂量依赖性地延长出血时间，在对照组中使出血时间延长两倍的剂量分别为>100和0.43 mg/kg。这些结果表明，与华法林相比，YM-75466的抗血栓形成作用与其对出血时间和凝血时间的影响明显不同。
