NO problem for nitroglycerin: Organic nitrate chemistry and therapy

Nitroglycerin (GTN) has been used clinically in the treatment of angina for over a century and is representative of the organic nitrates vasodilators. These are effective therapeutic agents that allow facile sublingual or transdermal administration. The vasodilatory mechanism involves activation of guanylate cyclase and is widely believed to involve biotransformation by chemical reaction of a nitrate with sulfhydryl or ferrous groups to yield nitric oxide. However, the chemistry of organic nitrates is poorly studied, provides scant support for these postulated reactions and provides a challenge for the chemist.