Abstract
Organic nitrates have been in therapeutic use for the treatment of angina pectoris for over a century. Recently it was reported that the release of nitric oxide (NO), mediated by a cascade of biochemical events, is responsible for the pharmacological activity of these compounds. The organic nitrates most commonly used, (glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and nicorandil), are useful for the treatment of stable, unstable and Prinzmetal's angina pectoris, for congestive heart failure and myocardial infarction. Nowadays new applications for these compounds, such as ocular hypotension and the protection of gastric mucosa, are emerging. However, the classical organic nitrates are characterized by undesirable side-effects, such as nitrate tolerance, strong_hypotension, reflex tachycardia and headaches. During the last decade, the search for new organic nitrates with reduced side effects and improved oral bioavailability has greatly intensified. The structural modifications studied in order to solve these problems and the structure-activity relationships for each new class of organic nitrates are reported in this review.
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