title: Novel anti-platelet agents: focus on thrombin receptor antagonists.
abstract: Platelets are the key in the pathogenesis of atherothrombotic disease such as acute coronary syndromes, stroke, and peripheral arterial disease. Current anti-platelet treatments are mainly based on inhibition of two important pathways of platelet activation: thromboxane A2 (TXA2) mediated (aspirin) and adenosine diphosphate (ADP)-P2Y12 receptor mediated (clopidogrel, prasugrel, and ticagrelor). Despite the dual anti-platelet therapy with aspirin and P2Y12 inhibitors have reduced ischemic events in patients with acute coronary syndromes (ACS), the rate of recurrent ischemic complication after ACS remains high. Combination of multiple anti-platelet agents is also associated with increased risk of bleeding. Thrombin is a potent platelet agonist and the increase of its activity has been reported in patients with ACS. Platelet effects of thrombin are mediated by protease-activated receptors (PAR), and PAR-1 is the most important receptor in human platelets. Two PAR-1 antagonists, vorapaxar and atopaxar, have undergone clinical investigation. In this review, we will describe the pharmacology of PAR-1 antagonists and will review and discuss results of randomized clinical trials with PAR-1 antagonists.
authors: Duke Clinical Research Institute, Durham, NC, USA. flavio.brito@duke.edu
authors: Flavio
authors: F
authors: de Souza Brito
authors: Pierluigi
authors: P
authors: Tricoci
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D007097:Imines / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use; D008024:Ligands; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D044463:Receptor, PAR-1 / Q000097:blood; D015398:Signal Transduction / Q000187:drug effects; D013917:Thrombin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C540445:E 5555; D007097:Imines; D007783:Lactones; D008024:Ligands; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044463:Receptor, PAR-1; D013917:Thrombin; C530299:vorapaxar