DRUG-INDUCED INHIBITION OF GUINEA PIG PLATELET AGGREGATION UNRELATED TO THEIR β-ADRENOLYTIC ACTIONS

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Inhibitory actions on adenosine diphosphate (ADP)-induced platelet aggregation of atenolol, dl- and d-D-32, IPS-339, pindolol and propranolol were investigated in guinea pigs for the purpose of obtaining a clue about a possible mechanism for the disaggregatory phenomenon of β-adrenoceptor blocking agents. The effects of verapamil and procaine on guinea pig platelet aggregation were also examined. All of these agents including verapamil and procaine showed a dose-dependent inhibitory effect on platelet aggregation, and their relative potencies determined on the basis of the molar concentrations producing a 50% inhibition of ADP-induced aggregation were in descending order: IPS-339>propranolol>verapamil>dl-D-32≈d-D-32>pindolol>procaine>atenolol. This order of relative potencies of the inhibitory actions of these test compounds on platelet aggregation was well correlated to those of local anaesthetic action in guinea pigs (r=0.932, P<0.01) and lipophilicity (r=-0.899, P<0.01), while it did not agree with the orders of potency of β-adrenoceptor blocking action, intrinsic sympathomimetic action and vasodilator action. From these results, it may be reasonable to propose that inhibitory actions of β-adrenoceptor blocking agents and local anaesthetics on platelet aggregation are caused through the same mechanism or through a very similar one.