化学
血小板
药理学
血小板聚集抑制剂
纤维蛋白原
抗血栓
离体
敌手
替罗非班
阿昔单抗
凝血酶
血小板活化
生物化学
体外
医学
内科学
受体
阿司匹林
经皮冠状动脉介入治疗
心肌梗塞
传统PCI
作者
Yumiko Moritani,Kazuo Sato,Takeshi Shigenaga,Nami Hisamichi,Masato Ichihara,Seijiro Akamatsu,Ken Suzuki,Tomoko Nii,Seiji Kaku,Tomihisa Kawasaki,Yuzo Matsumoto,Osamu Inagaki,K. Tomioka,Isao Yanagisawa
标识
DOI:10.1016/s0014-2999(02)01415-2
摘要
The pharmacological properties of YM-57029 [4-[4-(4-carbamimidoylphenyl)-3-oxopiperazin-1-yl]piperidino]acetic acid monohydrochloride trihydrate), a novel glycoprotein IIb/IIIa antagonist were examined in this study. YM-57029 inhibited fibrinogen binding to purified glycoprotein IIb/IIIa, 1000-fold more potently than the tetrapeptide arginine-glycine-aspartic acid-serine (RGDS). YM-57029 concentration-dependently inhibited ADP-, collagen- and high shear stress-induced platelet aggregation, strongly inhibited ATP release from platelets activated by ADP, and enhanced deaggregation of ADP-induced platelet aggregates. In a pro-aggregatory activity study, RGDS or SC-54701A ((S)-3-[3-[(4-amidinophenyl)carbamoyl]propionamido]-4-pentynoic acid monohydrochloride) caused prominent small aggregate formation. At a higher concentration, RGDS induced medium and large size aggregates, and SC-54701A induced medium aggregates. In contrast, YM-57029 produced only a few small and no larger size aggregates. Ex vivo ADP-induced platelet aggregation and platelet retention to collagen-coated plastic beads were dose-dependently inhibited by YM-57029 after intravenous bolus injection in guinea pigs. YM-57029 produced dose-dependent antithrombotic effects in carotid artery thrombosis and arterio-venous shunt thrombosis models in guinea pigs at 10 and 30 microg/kg, respectively. At these doses, YM-57029 prolonged template bleeding time. These results suggest that YM-57029 is a potent glycoprotein IIb/IIIa antagonist which has less pro-aggregatory effect. It may be a promising antiplatelet agent for thromboembolic diseases, and a good prototype for developing an orally active compound.
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