Drug-induced inhibition of guinea pig platelet aggregation unrelated to their beta-adrenolytic actions.

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 beta-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 greater than propranolol greater than verapamil greater than dl-D-32 not equal to d-D-32 greater than pindolol greater than procaine greater than 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 less than 0.01) and lipophilicity (r = -0.899, P less than 0.01), while it did not agree with the orders of potency of beta-adrenoceptor blocking action, intrinsic sympathomimetic action and vasodilator action. From these results, it may be reasonable to propose that inhibitory actions of beta-adrenoceptor blocking agents and local anaesthetics on platelet aggregation are caused through the same mechanism or through a very similar one.