Historical lessons in translational medicine: cyclooxygenase inhibition and P2Y12 antagonism

Circ Res. 2013 Jan 4;112(1):174-94. doi: 10.1161/CIRCRESAHA.111.300271.

Abstract

The development of drugs that inhibit platelets has been driven by a combination of clinical insights, fundamental science, and sheer luck. The process has evolved as the days of stumbling on therapeutic gems, such as aspirin, have long passed and have been replaced by an arduous process in which a drug is designed to target a specific protein implicated in a well-characterized pathophysiological process, or so we would like to believe. The development of antiplatelet therapy illustrates the importance of understanding the mechanisms of disease and the pharmacology of the compounds we develop, coupled with careful clinical experimentation and observation and, yes, still, a fair bit of luck.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aspirin / therapeutic use
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / history
  • Clopidogrel
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / history
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Discovery* / history
  • Drug Resistance
  • Evidence-Based Medicine
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Pharmacogenetics
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / history
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / history
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Translational Medical Research* / history

Substances

  • Cyclooxygenase Inhibitors
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticlopidine
  • Aspirin