Article: PDF OnlyEffects of a new platelet glycoprotein IIb/IIIa antagonist, SR121566, on platelet activation, platelet-leukocyte interaction and thrombin generationLi, N.; Wallen, N. H.; Savi, P.; Herault, J. P.; Herbert, J. M.Author Information N. Li and N. H. Wallén are with the Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden; P. Savi, J. P. Hérault, and J. M. Herbert are with Sanofi Recherche, Haemobiology Research Department, Toulouse, France. Blood Coagulation & Fibrinolysis: September 1998 - Volume 9 - Issue 6 - p 507-516 Buy Abstract The effects of SR121566, a new inhibitor of the glycoprotein (GP) IIb/IIIa complex on platelet activation and platelet-leukocyte interactions, as well as on thrombin generation were investigated. SR121566 dose-dependently inhibited adenosine diphosphate (ADP)-induced platelet fibrinogen binding determined either by flow cytometry analysis (IC50 = 50 nmol/l) or by measuring the binding of 125I-fibrinogen to activated human gel-filtered platelets (IC50 = 20 nmol/l). Consistent with its inhibitory effects on platelet fibrinogen binding, SR121566 demonstrated a dose-dependent inhibition of collagen-, ADP- or thrombin-induced platelet aggregation with IC50 values ranging between 20 and 60 nmol/l. SR121566, even tested at high concentrations, did not significantly affect ADP-induced platelet-leukocyte aggregate formation. The GPIIb/IIIa antagonist strongly inhibited thrombin generation in both native clotting blood and recalcified whole blood, suggesting that SR121566, by interfering with the platelet-activation events involved in facilitating thrombin generation, may also function as an anticoagulant, an effect which may contribute to its antithrombotic properties in humans. © 1998 Lippincott Williams & Wilkins, Inc.