ADP receptor antagonists as antiplatelet therapeutics

Expert Opin Emerg Drugs. 2003 May;8(1):93-101. doi: 10.1517/14728214.8.1.93.

Abstract

With the cloning of the P2Y12 receptor, the molecular basis for ADP-induced platelet aggregation is seemingly complete. Two platelet-bound ADP receptors, P2Y1 and P2Y12, operate through unique pathways to induce and sustain platelet aggregation via the glycoprotein (GP)IIb-IIIa integrin. P2Y1 operates via a glycoprotein q (Gq) pathway, activates phospholipase C, induces platelet shape change and is responsible for intracellular calcium mobilisation. P2Y12 inhibits adenylyl cyclase through a glycoprotein i (Gi)-dependent pathway, and is the target of the clinically used thienopyridines, ticlopidine (Ticlid, F. Hoffman-La Roche) and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Synthelabo). In addition, the receptor is targeted by the ADP analogue AR-C66096, which is currently in Phase IIb clinical trials, as well as other non-nucleoside-based preclinical leads.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2 Receptor Antagonists*
  • Receptors, Purinergic P2 / metabolism

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2