title: Historical lessons in translational medicine: cyclooxygenase inhibition and P2Y12 antagonism.
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 The process has evolved as the days of stumbling on therapeutic gems, such as aspirin, have long passed and have been replaced by an arduous process in which a drug is designed to target a specific protein implicated in a well-characterized pathophysiological process, or so we would like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.
authors.affiliation: UCD Conway Institute and Java Clinical Research, University College Dublin, Ireland.
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000266:history; D000077144:Clopidogrel; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000266:history; D004351:Drug Resistance; D019317:Evidence-Based Medicine; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D057170:Translational Research, Biomedical / Q000266:history
chemical_list: D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin