Lee H, Paton R C, Ruan C, Caen J P
Thromb Haemost. 1981 Oct;46(3):590-2.
The mode of action of the antiplatelet agent ticlopidine is not yet fully understood. Its multiple effects on platelet function include prolongation of the bleeding time, reduction in primary and secondary waves of ADP-induced aggregation and inhibition of collagen and thrombin-induced aggregation. We have studied the in vitro effects of ticlopidine on fibrinogen binding induced by ADP and adrenaline as well as factor VIII/vWF binding induced by ristocetin. 125I-fibrinogen binding was measured in suspensions of freshly-washed normal platelets stimulated by 10 microM ADP or 10 microM adrenaline. The binding of 125I-factor VIII/vWF in the presence of 1 mg/ml ristocetin was measured in both washed and paraformaldehyde-fixed platelets. Ticlopidine at final concentrations of 200, 100, 50 and 25 microM inhibited both ADP and adrenaline-induced fibrinogen binding in a dose-dependent manner. The mean % inhibition of ADP-induced fibrinogen binding was 82, 73, 42 and 32 respectively. The mean % inhibition of adrenaline-induced fibrinogen binding was 86, 82, 60 and 35 respectively. In contrast, the factor VIII/vWF binding was unaffected by ticlopidine at all concentrations except at 200 microM using fresh platelets where a slight inhibition (19%) was observed. These results suggest that ticlopidine either inhibits platelet activation and consequently fibrinogen binding, or inhibits the binding directly, presumably by having an effect on the specific configuration of the platelet membrane required for normal fibrinogen binding.
抗血小板药物噻氯匹定的作用机制尚未完全明确。它对血小板功能的多种影响包括延长出血时间、降低ADP诱导聚集的初级和次级波以及抑制胶原和凝血酶诱导的聚集。我们研究了噻氯匹定对ADP和肾上腺素诱导的纤维蛋白原结合以及瑞斯托菌素诱导的因子VIII/vWF结合的体外作用。在由10微摩尔ADP或10微摩尔肾上腺素刺激的新鲜洗涤正常血小板悬液中测量125I-纤维蛋白原结合。在洗涤血小板和多聚甲醛固定血小板中均测量了在1毫克/毫升瑞斯托菌素存在下125I-因子VIII/vWF的结合。终浓度为200、100、50和25微摩尔的噻氯匹定以剂量依赖方式抑制ADP和肾上腺素诱导的纤维蛋白原结合。ADP诱导的纤维蛋白原结合的平均抑制百分比分别为82%、73%、42%和32%。肾上腺素诱导的纤维蛋白原结合的平均抑制百分比分别为86%、82%、60%和35%。相比之下，除了使用新鲜血小板在200微摩尔时观察到轻微抑制（19%）外，噻氯匹定在所有浓度下对因子VIII/vWF结合均无影响。这些结果表明，噻氯匹定要么抑制血小板活化并因此抑制纤维蛋白原结合，要么直接抑制结合，推测是通过对正常纤维蛋白原结合所需的血小板膜特定构型产生影响。
