Shirakura S, Higo K, Takeda M, Karasawa A
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 1994 Jun;65(2):93-8. doi: 10.1254/jjp.65.93.
Antithrombotic effects of KW-3635, a newly synthesized thromboxane (TX) A2-receptor antagonist, were studied in guinea pigs. In the extracorporeal circulation thrombosis model, the shunt was filled with thrombi, and reduction of platelet count and increase in plasma TXA2 concentration were observed. KW-3635 (30 and 100 mg/kg, p.o.) inhibited the thrombus formation in the shunt and prevented the decrease in platelet count in the circulating blood without affecting the red blood cell count. BM13,505 (30, 100 mg/kg, p.o.), another TXA2-receptor antagonist, and ticlopidine (300 mg/kg, p.o.), an antiplatelet drug, also inhibited the thrombus formation, while aspirin (10, 300 mg/kg, p.o.) did not. Peripheral arterial occlusive disease was induced by injection of sodium laurate into the femoral artery in guinea pigs. Daily oral administration of KW-3635 (3-30 mg/kg) significantly prevented the progression of vascular lesions. BM13,505 (3-30 mg/kg, p.o.) and ticlopidine (100 mg/kg, p.o.) also ameliorated the vascular lesions, whereas aspirin (10, 100 mg/kg, p.o.) did not. KW-3635 at concentrations up to 10(-4) M did not affect coagulation parameters in vitro. These results suggest that TXA2 is involved in the pathogenesis of arterial thrombotic and ischemic disorders. KW-3635 may be useful for the treatment of thrombotic disease and peripheral arterial occlusive diseases.
在豚鼠中研究了新合成的血栓素（TX）A2受体拮抗剂KW-3635的抗血栓形成作用。在体外循环血栓形成模型中，分流器中充满血栓，观察到血小板计数减少和血浆TX A2浓度升高。KW-3635（30和100毫克/千克，口服）抑制分流器中的血栓形成，并防止循环血液中血小板计数减少，而不影响红细胞计数。另一种TX A2受体拮抗剂BM13,505（30、100毫克/千克，口服）和抗血小板药物噻氯匹定（300毫克/千克，口服）也抑制血栓形成，而阿司匹林（10、300毫克/千克，口服）则无此作用。通过向豚鼠股动脉注射月桂酸钠诱导外周动脉闭塞性疾病。每日口服KW-3635（3-30毫克/千克）可显著预防血管病变的进展。BM13,505（3-30毫克/千克，口服）和噻氯匹定（100毫克/千克，口服）也可改善血管病变，而阿司匹林（10、100毫克/千克，口服）则无此作用。浓度高达10(-4) M的KW-3635在体外不影响凝血参数。这些结果表明，TX A2参与动脉血栓形成和缺血性疾病的发病机制。KW-3635可能对治疗血栓性疾病和外周动脉闭塞性疾病有用。
