Antithrombotic Effect of a New Glycoprotein IIb/IIIa Antagonist, SC-52012A: Studies in two Guinea-pig Thrombosis Models

The antithrombotic effect of a new platelet membrane GPIIb/IIIa antagonist, SC-52012A together with the 5-HT(2) receptor antagonist, ketanserin was studied in two guinea-pig thrombosis models. A segment of the femoral artery was occluded by a platelet-rich thrombus following photochemical reaction between rose bengal and green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. SC-52012A, (1-10 μg/kg/min, intravenously (i.v.), dose-dependently prolonged the occlusion time of the artery. Ketanserin, (1 mg/kg, i.v.) or the cyclooxygenase inhibitor, aspirin (100 mg/kg, p.o.) produced no marked effect, but when ketanserin was combined with 3 μg/kg/min SC-52012A, the femoral artery occlusion time was strikingly greater than that produced by the same dose of SC-52012A. In the second model, an AV shunt was established between the carotid artery and the jugular vein and the platelet thrombus formed on a copper wire within the shunt was confirmed and quantified. SC-52012A (1-10 μg/kg/min) and ketanserin (1 mg/kg, i.v.), both produced a significant inhibitory effect on platelet thrombus formation in this model. As the expression of platelet membrane GPIIb/IIIa complex is the final step in the mechanism of platelet aggregation induced by most platelet agonists, inhibitors of this receptor complex may prove to be effective for the control of arterial thrombosis.