The effect of some epsilon-aminocaproic acid derivatives on platelet responses

ε-Aminocaproic acid (EACA) is a synthetic low molecular drug with antifibrinolytic activity. However, treatment with this drug can be incidentally associated with an in­creased thrombotic tendency. The aim of the present work was to test synthetic EACA derivatives for their antiplatelet activities. We investigated the effect of three EACA derivatives with antifibrinolytic activity: I. ε-aminocaproyl-L-leucine hydro­chloride (HCl*H-EACA-L-Leu-OH), II. ε-aminocaproyl-L-(S-benzyl)-cysteine hydrochlo­ride (HCl*H-EACA-L-Cys(S-Bzl)-OH) and III. ε-aminocaproyl-L-norleucine (H-EACA-L-Nle-OH) on platelet responses (aggregation and adhesion) and on their in­tegrity. It was found that: 1. as judged by LDH release test, none of the tested com­pounds, up to 20 mM, was toxic to platelets, 2. in comparison with EACA, all the syn­thetic derivatives inhibited much stronger the ADP- and collagen-induced aggrega­tion of platelets suspended in plasma (platelet rich plasma) and aggregation of these cells in whole blood, 3. EACA and its derivatives exerted a similar inhibitory effect on the thrombin-induced adhesion of platelets to fibrinogen-coated surfaces. Since platelet activation and blood coagulation are tightly associated processes, the antiplatelet properties of EACA derivatives are expected to indicate reduced throm- botic properties of these derivatives compared to EACA.