Antithrombotic effects of KBT-3022, a novel antiplatelet agent, in an arterial thrombosis model in the guinea-pig
✍ Scribed by Masamitsu Shimazawa; Yoshiharu Takiguchi; Kazuo Umemura; Mitsuyoshi Nakashima
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 171 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0272-4391
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✦ Synopsis
We examined the antithrombotic effect of KBT-3022, a novel antiplatelet agent, on photochemically induced arterial thrombosis in the guinea-pig saphenous artery, and compared its effect with that of aspirin and that of ticlopidine. Pretreatment with KBT-3022 [0.1 mg (0.2 µmole), 0.3 mg (0.7 µmole), 1 mg (2.2 µmole) and 3 mg (6.7 µmole)/kg, p.o.] 3 h prior to thrombosis induction prolonged the time required to achieve the thrombotic occlusion and inhibited the collagen (low concentration, 0.2 µg/ml; high concentration, 1 µg/ml)-induced platelet aggregation in whole blood ex vivo, each effect being concentration-dependent. The effects were tested of ticlopidine [30 mg (99.9 µmole), 100 mg (333.1 µmole) and 300 mg (999.2 µmole)/kg, p.o.] and aspirin [10 mg (55.5 µmole), 30 mg (166.5 µmole) and 100 mg (555.1 µmole)/kg, p.o.]. Both drugs prolonged the time to occlusion (but only at their highest concentration), and also inhibited the collagen (low concentration)-induced platelet aggregation in whole blood ex vivo. Aspirin [100 mg (555.1 µmole)/kg, p.o.], but not ticlopidine (at any concentration), inhibited the collagen (high concentration)-induced platelet aggregation. A good correlation was found between the antithrombotic and antiplatelet-aggregating effects of both KBT-3022 and aspirin, but not of ticlopidine. The antithrombotic potency of KBT-3022 was 300 times that of aspirin and 1000 times that of ticlopidine. These observations suggest that KBT-3022 may be clinically effective against platelet-rich thrombosis.