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Effects of Camonagrel, a Selective Inhibitor of Platelet Thromboxane Synthase, on the Platelet-Subendothelium Interaction

Villalobos M.A.a · De La Cruz J.P.b · Escalante R.a · Arrebola M.M.b · Guerrero A.b · Sánchez de la Cuesta F.b
Departments of aHuman Anatomy and bPharmacology and Therapeutics, University of Málaga, School of Medicine, Málaga, Spain Pharmacology 2003;69:44–50 (DOI:10.1159/000071266)

Abstract

The aim of this study was to compare the effects of a new thromboxane synthase inhibitor, camonagrel, on platelet aggregation and platelet-subendothelium interaction under flow conditions, in comparison with a standard thromboxane synthase inhibitor (dazoxiben) and a cyclooxygenase inhibitor (acetylsalicylic acid). With respect to platelet aggregation in whole blood, the 50% inhibitory concentrations (IC50) of camonagrel were between 318 and 797 µmol/l after induction with collagen and adenosine 5′-diphosphate, respectively. For inhibition of thromboxane B2 synthesis, the IC50 values were 868 ± 68 µmol/l; prostaglandin E2 was inhibited only by acetylsalicylic acid (IC50 for camonagrel >2,000 µmol/l), and the leukocyte 6-keto-PGF level was increased by camonagrel. The greatest reduction in percentage subendothelial surface occupied by platelets (mainly in the thrombi) after blood perfusion was seen after incubation with camonagrel in the range of concentrations that inhibited collagen-induced platelet aggregation. In conclusion, camonagrel reduced platelet-subendothelium interaction under flow conditions, showing this effect in a range of concentrations lower than in inhibition of platelet aggregation.

 

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