Thrombin receptor antagonists as novel therapeutic targets

Curr Opin Drug Discov Devel. 2001 Jul;4(4):417-27.


In addition to its pivotal role in hemostasis, thrombin activates various cell types such as platelets and vascular smooth muscle cells via proteolytic processing of specific cell-surface receptors known as proteinase activated receptors (PARs), the prototype of which is PAR-1. Thrombin receptor activation is likely to play a key role in cardiovascular disorders such as arterial thrombosis, atherosclerosis and restenosis, and as such a thrombin receptor antagonist should have potential utility in the treatment of these disorders. Since the fibrin pathway is unaffected by thrombin receptor antagonism, a thrombin receptor antagonist is expected to have minimal bleeding liability, which is a complicating factor in existing antithrombotic therapy. The currently available collection of thrombin receptor antagonists fall into three categories: (i) peptide antagonists; (ii) peptidomimetics; and (iii) non-peptide thrombin receptor antagonists, and this review outlines the development of members of these classes.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Receptors, Thrombin / antagonists & inhibitors*
  • Receptors, Thrombin / metabolism


  • Fibrinolytic Agents
  • Receptors, Thrombin