Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands.
Expert Rev Clin Pharmacol. 2010 Mar;3(2):177-82. doi: 10.1586/ecp.10.2.
Upon erosion and rupture of an atherosclerotic plaque, collagen and serotonin (5-hydroxytyramine [5-HT]) induce a process of simultaneous platelet aggregation and vasoconstriction. Simultaneous inhibition of these pathophysiological processes, attainable by 5-HT inhibition, is a potential drug target and could offer an attractive treatment modality. The availability of a reliable and accurate test to measure inhibition of 5-HT-induced platelet aggregation would facilitate the rational development of such new compounds. Therefore, we developed a validated method to measure the additive effect of 5-HT on platelet aggregation in human whole blood after an initial induction by a low-concentration collagen, using impedance aggregometry. This method is feasible to measure 5-HT-induced platelet aggregation in whole blood for the evaluation of promising platelet aggregation inhibitors possessing 5-HT antagonistic activity. The availability of this method will support and stimulate selective 5-HT antagonism as effective management of thrombosis.
在动脉粥样硬化斑块侵蚀和破裂时,胶原和血清素(5-羟色胺[5-HT])会引发血小板聚集和血管收缩的同时发生。通过抑制 5-HT 来同时抑制这些病理生理过程是一个潜在的药物靶点,并可能提供一种有吸引力的治疗方式。一种可靠和准确的测试方法来测量 5-HT 诱导的血小板聚集抑制作用,将有助于这些新型化合物的合理开发。因此,我们使用阻抗聚集仪,开发了一种经过验证的方法来测量在初始低浓度胶原诱导后,5-HT 对人全血中血小板聚集的附加作用。该方法可用于测量全血中 5-HT 诱导的血小板聚集,以评估具有 5-HT 拮抗活性的有前途的血小板聚集抑制剂。该方法的出现将支持和刺激作为血栓有效管理的选择性 5-HT 拮抗作用。