EFFECTS OF A NEW PLATELET GLYCOPROTEIN IIB IIIA ANTAGONIST, SR121566,ON PLATELET ACTIVATION, PLATELET-LEUKOCYTE INTERACTION AND THROMBIN GENERATION/

The effects of SR121566, a new inhibitor of the glycoprotein (GP) IIb/ IIIa complex on platelet activation and platelet-leukocyte interaction s, as well as on thrombin generation were investigated. SR121566 dose- dependently inhibited adenosine diphosphate (ADP)-induced platelet fib rinogen binding determined either by flow cytometry analysis (IC50 = 5 0 nmol/l) or by measuring the binding of I-125-fibrinogen to activated human gel-filtered platelets (IC50 = 20 nmol/l). Consistent with its inhibitory effects on platelet fibrinogen binding, SR121566 demonstrat ed 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/I IIa antagonist strongly inhibited thrombin generation in both native c lotting blood and recalcified whole blood, suggesting that SR121566, b y interfering with the platelet-activation events involved in facilita ting thrombin generation, may also function as an anticoagulant, an ef fect which may contribute to its antithrombotic properties in humans. Blood Coag Fibrinol 9:507-515 (C) 1998 Lippincott Williams & Wilkins.