TP receptor antagonism: a new concept in atherothrombosis and stroke prevention.
Conventional antiplatelet agents such as aspirin, ticlopidine, and clopidogrel are currently used in the prevention of cardiovascular and cerebrovascular events. However, side effects such as bleeding complications and gastrointestinal disorders and, in some patients, resistance have made the development of new agents desirable. Recently, thromboxane receptors (thromboxane and prostaglandin endoperoxide PGG2-PGH2 receptors) called TP receptors have received increasing attention. These receptors are membrane-bound G-coupled receptors found not only on platelets but also on macrophages, monocytes, vascular endothelial cells, and smooth muscle cells. Antagonists of TP receptors have advantages over aspirin as they not only block the effect of thromboxane A2 on platelets, but also inhibit other ligands such as prostaglandin endoperoxides and isoprostanes. Given the distribution of TP receptors in platelets, in circulating inflammatory cells, in the vascular wall and in atherosclerotic plaques, they also inhibit the effects of thromboxane A2 over TP receptors on vascular cells or in the plaque. Terutroban (Triplion or S18886), a new oral specific TP receptor antagonist, has, aside from being an antithrombotic agent, important vascular properties. It improves endothelial function and has an antiatherosclerotic effect. The potential therapeutic applications of terutroban in the prevention of atherothrombosis, particularly in the cerebrovascular and cardiovascular fields including stroke and coronary artery disease, are based on a number of convincing experimental animal and clinical studies. A large trial is currently comparing the efficacy and safety of terutroban versus aspirin in secondary prevention of cardiovascular events in patients who have suffered a stroke or transient ischemic attack (PERFORM Study).
Chamorro
Angel
A
Hospital Clinic of Barcelona, Department of Neurosciences, 170 Villarroel, Barcelona ES-08036, Spain. achamorro@ub.edu
D050197:Atherosclerosis / Q000150:complications*; D006801:Humans; D009281:Naphthalenes / Q000627:therapeutic use*; D011422:Propionates / Q000627:therapeutic use*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*
D009281:Naphthalenes; D011422:Propionates; D017482:Receptors, Thromboxane; C501362:terutroban