Summary
In order 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 inhibitors, 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 active 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.
