Onoda J M, Sloane B F, Honn K V
Thromb Res. 1984 Jun 1;34(5):367-78. doi: 10.1016/0049-3848(84)90241-x.
Four calcium channel blockers (nimodipine, nifedipine, verapamil and diltiazem) of three chemical classes were tested in vitro for inhibition of platelet aggregation using heparinized human platelet rich plasma. Both ADP- and thrombin-induced aggregation were inhibited as was the biosynthesis of thromboxane A2 in response to ADP or thrombin. However, the IC50's for the calcium channel blockers were greater than or equal to 110 microM. Nimodipine was also tested in combination with prostacyclin, the potent platelet antiaggregatory agent, or with a thromboxane synthase inhibitor, U63557A. At concentrations at which neither nimodipine or prostacyclin inhibited platelet aggregation greater than or equal to 10%, the two compounds is combination synergistically inhibited both ADP- and thrombin-induced platelet aggregation. U63557A inhibited biosynthesis of thromboxane A2 by platelets in response to ADP or thrombin, but did not inhibit either ADP- or thrombin-induced platelet aggregation. However, U63557A in combination with a threshold inhibitory concentration of nimodipine resulted in a synergistic inhibition of platelet aggregation induced by ADP or thrombin. These results suggest that calcium channel blockers may be of therapeutic value as a new class of antithrombogenic agents when used in combination with agents that inhibit either platelet aggregation or synthesis of platelet thromboxane A2.
使用肝素化的富含人血小板的血浆，在体外对三种化学类别的四种钙通道阻滞剂（尼莫地平、硝苯地平、维拉帕米和地尔硫䓬）进行了抑制血小板聚集的测试。ADP和凝血酶诱导的聚集均受到抑制，对ADP或凝血酶的反应中血栓素A2的生物合成也受到抑制。然而，钙通道阻滞剂的IC50大于或等于110微摩尔。尼莫地平还与强效血小板抗聚集剂前列环素或血栓素合酶抑制剂U63557A联合进行了测试。在尼莫地平和前列环素均未抑制血小板聚集超过或等于10%的浓度下，这两种化合物联合使用可协同抑制ADP和凝血酶诱导的血小板聚集。U63557A抑制血小板对ADP或凝血酶反应中血栓素A2的生物合成，但不抑制ADP或凝血酶诱导的血小板聚集。然而，U63557A与阈值抑制浓度的尼莫地平联合使用可协同抑制ADP或凝血酶诱导的血小板聚集。这些结果表明，当钙通道阻滞剂与抑制血小板聚集或血小板血栓素A2合成的药物联合使用时，可能作为一类新的抗血栓形成药物具有治疗价值。
