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

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.

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.

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.

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.

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.