title: In vitro effects of clopidogrel on the platelet-subendothelium interaction, platelet thromboxane and endothelial prostacyclin production, and nitric oxide synthesis.
abstract: Clopidogrel is an antiplatelet drug that belongs to the group of thienopyridines. Because of its main mechanism of action most studies of clopidogrel have centered on the platelet ADP pathway. The aim of the present study was to compare the effects of clopidogrel, ticlopidine, and aspirin, on platelet activation by collagen (the main inducer of platelet activation in vivo), prostanoid, and NO production, and the effects on blood perfusion experiments. Clopidogrel inhibited platelet aggregation induced in whole blood by collagen and TxB2 production to a greater extent than did ticlopidine. Prostacyclin synthesis did not change after incubation with thienopyridines, whereas aspirin inhibited synthesis in a dose-dependent manner. Thienopyridines increased NO production to a greater extent than did aspirin. All three drugs impaired the platelet-subendothelium interaction under flow conditions. With thienopyridines, the presence of endothelium did not modify the percentage of the surface coated by platelets.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: María Monsalud
authors.initials: MM
authors.lastname: Arrebola
authors.forename: José Pedro
authors.initials: JP
authors.lastname: De la Cruz
authors.forename: María Auxiliadora
authors.initials: MA
authors.lastname: Villalobos
authors.forename: Araceli
authors.initials: A
authors.lastname: Pinacho
authors.forename: Ana
authors.initials: A
authors.lastname: Guerrero
authors.forename: Felipe
authors.initials: F
authors.lastname: Sánchez de la Cuesta
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D000077144:Clopidogrel; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D013929:Thromboxane B2; D000077144:Clopidogrel; D011464:Epoprostenol; D013988:Ticlopidine; D001241:Aspirin