Umetsu T, Sanai K
Thromb Haemost. 1978 Feb 28;39(1):74-83.
In ordder to evaluate 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) as a possible antithrombotic compound, a simple and reproducible method for experimental thrombosis in rats was devised. A silken thread was inserted in the extracorporeal shunt between the carotid artery and the jugular vein. 15 min after the circulation of blood, wet weight of thrombus which developed on the thread was measured to determine the degree and rate of thrombus formation. Equalization of average body weight of rats for each group provided good reproducibility. Microscopic examination demonstrated that the thrombus was primarily composed of platelets. By use of the technique, the activities of KC-6141 and two known inhbitors, aspirin and dipyridamole, were determined. Of the three compounds, KC-6141 was the most potent inhibitor for the thrombosis. Its ED50 was 60 mg/kg when given orally and the compound was activite for about 40 hr. Aspirin was about twice as less active than KC-6141 and dipyridamole showed no effect on the thrombosis. The ranking order of potency against the experimental thrombosis for the three compounds was the same as that for inhibition of platelet aggregation in vitro and platelet retention in rats, as reported previously by us. Therefore the method seems to be associated with platelet aggregation and retention. The above result suggests that KC-6141 is of value as antithrombotic drug in vivo.
为了评估1-甲基-2-巯基-5-(3-吡啶基)-咪唑(KC-6141)作为一种可能的抗血栓形成化合物，设计了一种简单且可重复的大鼠实验性血栓形成方法。将丝线插入颈动脉和颈静脉之间的体外分流管中。血液循环15分钟后，测量丝线上形成的血栓湿重，以确定血栓形成的程度和速率。使每组大鼠的平均体重相等可提供良好的重复性。显微镜检查表明，血栓主要由血小板组成。通过使用该技术，测定了KC-6141以及两种已知抑制剂阿司匹林和双嘧达莫的活性。在这三种化合物中，KC-6141是最有效的血栓形成抑制剂。口服时其半数有效剂量(ED50)为60mg/kg，该化合物的活性持续约40小时。阿司匹林的活性约为KC-6141的一半，双嘧达莫对血栓形成无影响。这三种化合物对实验性血栓形成的效力排序与我们之前报道的对体外血小板聚集和大鼠体内血小板滞留的抑制作用排序相同。因此，该方法似乎与血小板聚集和滞留有关。上述结果表明，KC-6141在体内作为抗血栓药物具有价值。
