Progress in the field of GPIIb/IIIa antagonists.
Platelet aggregation plays an important role in pathological situations such as myocardial infarction, unstable angina, peripheral artery disease, and stroke. Thus, pharmacological agents that specifically inhibit platelet aggregation are of great interest in the treatment and prevention of these cardiovascular diseases. Since binding of activated glycoprotein IIb/IIIa complex, a platelet surface integrin, to fibrinogen is the final step leading to platelet aggregation regardless of the initial stimulus, many researches have focused on the development of drugs that could antagonize this integrin. Three intravenous glycoprotein IIb/IIIa antagonists are currently marketed for the prevention of myocardial infarction in patients undergoing percutaneous intervention: Abciximab, Eptifibatide and Tirofiban. To further test the clinical efficacy of these agents, oral glycoprotein IIb/IIIa antagonists have been developed but only led to disappointing clinical results. Nevertheless, due to recognized usefulness of oral agents for the prevention and treatment of cardiovascular diseases, a great number of new orally active compounds are under clinical or preclinical evaluation. The aim of this review is to describe the chemical, pharmacological and clinical properties of existing and forthcoming glycoprotein IIb/IIIa antagonists.
Natural and Synthetic Drugs Research Centre, Department of Medicinal Chemistry, University of Liège, 1, av. de l'Hôpital, B36 Sart-Tilman, B-4000 Liège, Belgium.
Julien
J
Hanson
Xavier
X
de Leval
Jean-Louis
JL
David
Claudiu
C
Supuran
Bernard
B
Pirotte
Jean-Michel
JM
Dogné
D000284:Administration, Oral; D000818:Animals; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007275:Injections, Intravenous; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex