卡维地洛——一种对人体血小板具有显著抗聚集作用的β受体阻滞剂。

Carvedilol--a beta-blocker with considerable antiaggregatory effect on human blood platelets.

作者信息

Petrikova M, Jancinova V, Nosal R, Majekova M, Fabryova V

机构信息

Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.

出版信息

Bratisl Lek Listy. 2005;106(1):20-5.

PMID:15869009

Abstract

BACKGROUND

Activated blood platelets play a key role in the genesis of many pathological states. Several studies have documented that beta-blockers can influence platelet aggregation. Carvedilol, a third generation non-selective agent with vasodilatory properties, is successfully used in pathological states accompanied with platelet hyperreactivity, however information on its antiplatelet activity is lacking.

OBJECTIVES

The aim of this study was to analyse the in vitro effect of carvedilol on aggregation of human blood platelets, to compare this effect with the effect of propranolol and atenolol, and to determine whether its suggested antiaggregatory effect was accompanied with reduced thromboxane B2 formation. Moreover, some physico-chemical parameters of the drugs tested were calculated and compared.

METHODS

Platelets were isolated by differential centrifugation and platelet aggregation was measured by the turbidimetric method. The amount of thromboxane B2 was measured by the radioimmunoassay method. Physico-chemical parameters of the drugs tested were calculated using the computer programme Hyperchem.

RESULTS

Carvedilol and propranolol inhibited platelet aggregation in the rank order of stimuli: PMA > thrombin > A23187 > epinephrine. The reduction was accompanied by inhibition of thromboxane B2 formation. In comparison to propranolol, carvedilol was more effective, with the exception for aggregation stimulated with ADP. Atenolol did not affect any platelet function tested. From the drugs studied, the molecule of carvedilol was found to possess the highest partition coefficient, the highest index of molar refractivity, and the lowest dipole moment.

CONCLUSION

Our study found carvedilol to be more potent than propranolol and atenolol in inhibiting platelet aggregation and thromboxane B2 production. This may be due to the different structure and more convenient physico-chemical parameters of the carvedilol molecule.

摘要

背景

活化的血小板在多种病理状态的发生中起关键作用。多项研究表明β受体阻滞剂可影响血小板聚集。卡维地洛是一种具有血管舒张特性的第三代非选择性药物，已成功用于伴有血小板高反应性的病理状态，但关于其抗血小板活性的信息尚缺乏。

目的

本研究旨在分析卡维地洛对人血小板聚集的体外作用，将其与普萘洛尔和阿替洛尔的作用进行比较，并确定其推测的抗聚集作用是否伴随着血栓素B2生成的减少。此外，还计算并比较了所测试药物的一些物理化学参数。

方法

通过差速离心法分离血小板，采用比浊法测定血小板聚集。采用放射免疫分析法测定血栓素B2的含量。使用计算机程序Hyperchem计算所测试药物的物理化学参数。

结果

卡维地洛和普萘洛尔抑制血小板聚集的程度依次为：佛波酯＞凝血酶＞A23187＞肾上腺素。这种减少伴随着血栓素B2生成的抑制。与普萘洛尔相比，卡维地洛除对ADP刺激的聚集外更有效。阿替洛尔对所测试的任何血小板功能均无影响。在所研究的药物中，发现卡维地洛分子具有最高的分配系数、最高的摩尔折射率指数和最低的偶极矩。