Antithrombotic effects of T-250, a novel GPIIb/IIIa antagonist, in thrombosis models

• Published in: Japanese Journal of Pharmacology Vol. 76; no. suppl.1; p. 175
• Main Authors: Yoshinobu Izumi, Hidetoshi Kaga, Kazumi Maeda, Masami Chikazawa, Tetsuo Fukushima, Satoshi Ono
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1998
• ISSN: 0021-5198; 1347-3506

The antithrombotic effects of T-250, a novel GPIIb/IIIa antagonist, were investigated in two thrombosis models. T-250 showed a dose-dependent inhibition of ex vivo ADP-induced platelet aggregation after i.v. bolus (0.1-0.3 mg/kg) and p.o. (1-10 mg/kg) administration in dogs. In a rabbit model of cyclical flow reductions (CERs) induced by pinching and stenosis in carotid artery, T-250 (0.003-0.3 mg/kg i.v.) abolished the CFRs dosedependently. Aspirin (1-10 mg/kg i.v.) showed a marginal effect on abolition of CRFs. In a dog model of left circumflex coronary artery occlusive thrombosis induced by electrical injury and critical stenosis, 6-hr continuous i.v. infusion of 0.6 μg/kg/min of T-250 significantly increased time to occlusion without causing prolongation of bleeding time. At this dose, ex vivo ADP- and collagen-induced platelet aggregation were inhibited by >93% and >65%, respectively. Thus, T-250 prevented coronary artery thrombosis with moderate inhibition of platelet aggregation. T-250 may have therapeutic potential as an effective antithrombotic agent.