Mikashima H, Ochi H, Muramoto Y, Yasuda H, Tsuruta M, Maruyama Y
Thromb Res. 1986 Aug 15;43(4):455-68. doi: 10.1016/0049-3848(86)90090-3.
Effects of a new imidazole derivative, sodium 4-[alpha-hydroxy-5-(imidazolyl)-2-methylbenzyl]-3,5-dimethyl benzoate dihydrate (Y-20811), on thromboxane (TX) production and platelet aggregation were investigated. Y-20811 inhibited TX synthetase (IC50 = 2.2 X 10(-8) M) and platelet aggregation induced by arachidonic acid (AA) in human, guinea pig and rabbit platelets in vitro. Administered orally to rabbits, Y-20811 at a dose of 1 mg/kg decreased serum TXB2 concomitant with increasing 6-keto PGF1 alpha and at a dose of 3 mg/kg inhibited AA-induced platelet aggregation, in both cases for at least 48 hours. Y-20811 (0.3 mg/kg/day) administered to rabbits for 7 days decreased serum TXB2 levels by 50-90% during the medication, and these levels were restored to initial values 3 days after withdrawal of the drug. At a dose of 1 mg/kg Y-20811 protected rabbits against death induced by AA (2 mg/kg). These results indicate that Y-20811 is a selective and long-lasting TX synthetase inhibitor and an anti-aggregating agent useful in preventing thrombotic disorders.
研究了一种新型咪唑衍生物4-[α-羟基-5-(咪唑基)-2-甲基苄基]-3,5-二甲基苯甲酸钠二水合物（Y-20811）对血栓素（TX）生成和血小板聚集的影响。Y-20811在体外对人、豚鼠和兔血小板中的TX合成酶具有抑制作用（IC50 = 2.2×10⁻⁸ M），并能抑制花生四烯酸（AA）诱导的血小板聚集。给兔口服Y-20811，剂量为1 mg/kg时可降低血清TXB2水平，同时6-酮-PGF1α水平升高；剂量为3 mg/kg时可抑制AA诱导的血小板聚集，两种情况下作用至少持续48小时。给兔连续7天给予Y-20811（0.3 mg/kg/天），给药期间血清TXB2水平降低50 - 90%，停药3天后这些水平恢复到初始值。剂量为1 mg/kg时，Y-20811可保护兔免受AA（2 mg/kg）诱导的死亡。这些结果表明，Y-20811是一种选择性且长效的TX合成酶抑制剂和抗聚集剂，可用于预防血栓性疾病。
