Pawlak D, Pawlak K, Chabielska E, Małyszko J, Takada A, Myśliwiec M, Buczko W
Department of Pharmacodynamics, Medical Academy, Białystok, Poland.
Thromb Res. 1998 Jun 15;90(6):259-70. doi: 10.1016/s0049-3848(98)00037-1.
In our study, we demonstrated that DV-7028: (3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6, 7,8,9-tetrahydro-2H-pyrido [1,2,-a]-1,3,5-triazine-2, 4(3H)-dione maleate)--a selective 5-HT2A receptor antagonist, inhibited thrombus formation in the arterial thrombosis model and was completely ineffective in the prevention of venous thrombosis in the rat. In washed platelets prelabelled with 3H-serotonin, DV-7028 inhibited, in a dose-dependent manner, the collagen-induced secretion of serotonin. However, the uptake of serotonin into platelets was not affected by this substance. Administration of DV-7028 also inhibited platelet aggregation in the whole blood and platelet-rich plasma (PRP) induced by collagen, and diminished serotonin-induced aggregation of rat platelets in the presence of a sensitizing but nonaggregating amount of ADP, whereas it did not modify aggregation in PRP when induced by ADP. DV-7028 caused a concentration-dependent, almost parallel shift to the right of the concentration-response to serotonin for its pressor effect in the rat perfused tail artery. The present data demonstrate that DV-7028 exhibits 5-HT2A receptor antagonistic properties in the rat cardiovascular system, exhibits antithrombotic effect in the model of arterial but not venous thrombosis in rats. These results constitute further evidence of the possible importance of serotonin as a mediator of platelet thrombosis in arteries. Moreover, they can provide a useful tool for the prevention of various thrombotic diseases.
在我们的研究中，我们证明了DV - 7028：（3 - [2 - [4 - （4 - 氟苯甲酰基）哌啶 - 1 - 基]乙基] - 6,7,8,9 - 四氢 - 2H - 吡啶并[1,2 - a] - 1,3,5 - 三嗪 - 2,4（3H） - 二酮马来酸盐）——一种选择性5 - HT2A受体拮抗剂，在动脉血栓形成模型中抑制血栓形成，而在预防大鼠静脉血栓形成方面完全无效。在用3H - 5 - 羟色胺预标记的洗涤血小板中，DV - 7028以剂量依赖性方式抑制胶原诱导的5 - 羟色胺分泌。然而，5 - 羟色胺摄取到血小板中不受该物质影响。给予DV - 7028还抑制全血和富含血小板血浆（PRP）中胶原诱导的血小板聚集，并在存在致敏但不聚集量的ADP时减少5 - 羟色胺诱导的大鼠血小板聚集，而当由ADP诱导时它不改变PRP中的聚集。DV - 7028在大鼠灌注尾动脉中对其升压作用导致对5 - 羟色胺的浓度 - 反应呈浓度依赖性、几乎平行地向右移动。目前的数据表明，DV - 7028在大鼠心血管系统中表现出5 - HT2A受体拮抗特性，在大鼠动脉而非静脉血栓形成模型中表现出抗血栓作用。这些结果进一步证明了5 - 羟色胺作为动脉中血小板血栓形成介质的可能重要性。此外，它们可为预防各种血栓性疾病提供有用的工具。
