Aernoud Fiolet

35 General introduction and thesis outline Table 1. Examples of drugs that have been repurposed. Generic drug name Brand name Original indication Repurposed use Allopurinol Acepurin,® Zyloric® Antineoplastic Gout Amantadine Symmetrel ® Influenza Parkinson’s disease, essential tremor Atomoxetine Strattera® Antidepressant Attention deficit hyperactivity disorder Acetylsalicylic acid Aspirin® Antipyretic, anti- inflammatory Antithrombotic treatment Bevacizumab Avastin® Metastatic colon and non- small cell lung cancer Exudative (wet) macular degeneration Bimatoprost Lumigan®, Ganmono® Glaucoma Eyelash growth Bromocriptine Parlodel® Parkinson’s disease Hyperprolactinemia Bupropion Wellbutrin XR®, Zyban® Antidepressant Smoking cessation Erytromycin Erythrocin® Antibiotic Gastropareses Dapagliflozin, Empagliflozin Farxiga®, Forxiga®, Jardiance® Diabetes Heart failure Metoclopramide Primperan® Gastro-oesophageal reflux Migraine Thalidomide Softenon®, Contergan®, Thalomid® Sedation Multiple myeloma 6-Thioguanine Thiosix® Leukemia Colitis ulcerosa These examples show how in some cases new indications or targets for compounds or drugs are found by coincidence. However, the structural characteristics or biological effects of a drug can also on beforehand be indicative of other possible uses. An example of rediscovering drugs in such way is the route of the monoclonal antibody bevacizumab. 121 Bevacizumab was originally developed to treat patients withmetastatic colon cancer andnon-small cell lung cancer. Itsmechanismof action comes from inhibiting vascular endothelial growth factor and hereby inhibiting angiogenesis, preventing vascularisation of the tumour. However, currently the drug is used in the treatment of abnormal vascularisation of the retina in exudative (wet) macular degeneration. 125 One of the most important repurposed drugs in cardiovascular medicine is acetylsalicylic acid; which was originally used for its antipyretic and anti-inflammatory properties, but is currently widely used in low- doses as antithrombotic drug in atherosclerosis. 126