Biochemical and pharmacological properties of clopidogrel: a new ADP receptor antagonist

Clopidogrel is a novel platelet ADP receptor antagonist. Animal experiments have shown that clopidogrel's antiaggregating activity is due to a short-l asting metabolite generated in the liver by a cytochrome P-450-dependent pa thway. The active metabolite of clopidogrel antagonizes a set of low-affini ty ADP receptors on platelets. Thus, clopidogrel therapy inhibits adenylyl cyclase down regulation, protein phosphorylation at tyrosine residues, Gp I Ib/IIIa complex activation, and fibrinogen binding, aggregation and release . This suggests that these processes are mediated by activation of the low- affinity ADP receptor. Clopidogrel therapy reduces the platelet aggregation and myointimal thickening that occur following endothelial injury of the r abbit carotid artery. The antithrombotic activity of clopidogrel is several times greater than that of ticlopidine and aspirin in animal models of art erial and venous thrombosis. Clopidogrel is more effective than aspirin and has a favourable safety and tolerability profile; thus, it is a promising and potent antithrombotic therapy.