Perzborn E, Fiedler V B, Seuter F, Stasch J P, Weber H, Sander E, Böshagen H, Rosentreter U
Institute of Pharmacology, Bayer AG, Wuppertal, FRG.
Stroke. 1990 Dec;21(12 Suppl):IV143-5.
The thromboxane A2-receptor antagonistic properties of Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbaz o-lepropanoic acid] have been evaluated in various pharmacologic models. Bay U 3405 specifically inhibits platelet aggregation induced by U 46619, collagen, platelet-activating factor, and the second wave of ADP (IC50 0.5, 0.07, 0.3, 0.19 microM) in human plasma. The plasma phase of ADP-induced aggregation is not affected. U 46619-induced platelet aggregation is competitively antagonized (pA2 = 6.3). In humans, ex vivo platelet aggregation is inhibited after oral application of 2 or 50 mg Bay U 3405. Bay U 3405 also specifically and competitively antagonizes U 46619-induced contractions of rabbit aortic rings (pA2 = 7.4). In vivo, Bay U 3405 protects rabbits dose dependently from arachidonic acid or collagen-induced thromboembolism (ED50 1-3 mg/kg p.o). Chronic administration of Bay U 3405 to stroke-prone spontaneously hypertensive rats reduces stroke-related mortality and diminishes the occurrence of cerebral hemorrhages. From these results, we conclude that Bay U 3405 is an orally active, selective, and competitive thromboxane A2-receptor antagonist that may be beneficial in the treatment of cardiovascular or cerebrovascular diseases.
已在多种药理模型中评估了Bay U 3405[（3R）-3-（4-氟苯基磺酰胺基）-1,2,3,4-四氢-9-咔唑丙酸]的血栓素A2受体拮抗特性。Bay U 3405能特异性抑制人血浆中由U 46619、胶原、血小板活化因子及第二波ADP诱导的血小板聚集（IC50分别为0.5、0.07、0.3、0.19微摩尔）。ADP诱导聚集的血浆期不受影响。U 46619诱导的血小板聚集受到竞争性拮抗（pA2 = 6.3）。在人体中，口服2或50毫克Bay U 3405后，离体血小板聚集受到抑制。Bay U 3405还能特异性且竞争性地拮抗U 46619诱导的兔主动脉环收缩（pA2 = 7.4）。在体内，Bay U 3405能剂量依赖性地保护兔免受花生四烯酸或胶原诱导的血栓栓塞（口服ED50为1 - 3毫克/千克）。对易中风自发性高血压大鼠长期给予Bay U 3405可降低与中风相关的死亡率，并减少脑出血的发生。从这些结果来看，我们得出结论，Bay U 3405是一种口服活性、选择性且竞争性的血栓素A2受体拮抗剂，可能对心血管或脑血管疾病的治疗有益。
