Takiguchi Y, Wada K, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Thromb Haemost. 1992 Oct 5;68(4):460-3.
The antithrombotic effect of the thromboxane A2 receptor antagonist, vapiprost, was compared with those of other antiplatelet drugs using an arterial thrombosis model which utilized photochemical reaction in the rat femoral artery. Vapiprost prolonged the time required to occlude the artery with thrombus and inhibited collagen-induced rat platelet aggregation in whole blood ex vivo, in a dose-dependent manner. The potency ranking of antithrombotic effect was vapiprost > ketanserin (serotonin 5-HT2 receptor antagonist) >> ticlopidine (inhibitor of ADP-induced platelet aggregation) = dipyridamole (adenosine uptake inhibitor) > aspirin (cyclooxygenase inhibitor). On the other hand, the ranking of antiplatelet effect was ticlopidine > or = vapiprost > or = aspirin. Ketanserin and dipyridamole were ineffective. Relative to their antiplatelet effect, vapiprost and ketanserin had powerful antithrombotic effects. It is possible that the potent antithrombotic effects of vapiprost and ketanserin in vivo reflect the ability of these drugs to inhibit mediator-induced vascular contractions in addition to platelet aggregation. The results of the present study also suggest that TXA2 may play an important role in thrombogenesis in rats.
使用利用大鼠股动脉光化学反应的动脉血栓形成模型，将血栓素A2受体拮抗剂瓦吡前列素的抗血栓形成作用与其他抗血小板药物的作用进行了比较。瓦吡前列素以剂量依赖性方式延长了血栓阻塞动脉所需的时间，并在体外全血中抑制了胶原诱导的大鼠血小板聚集。抗血栓形成作用的效力排名为瓦吡前列素>酮色林（5-羟色胺5-HT2受体拮抗剂）>>噻氯匹定（ADP诱导的血小板聚集抑制剂）=双嘧达莫（腺苷摄取抑制剂）>阿司匹林（环氧化酶抑制剂）。另一方面，抗血小板作用的排名为噻氯匹定>或=瓦吡前列素>或=阿司匹林。酮色林和双嘧达莫无效。相对于它们的抗血小板作用，瓦吡前列素和酮色林具有强大的抗血栓形成作用。瓦吡前列素和酮色林在体内的强效抗血栓形成作用可能反映了这些药物除抑制血小板聚集外还能抑制介质诱导的血管收缩的能力。本研究结果还表明，TXA2可能在大鼠血栓形成中起重要作用。
