Molecule Monday: Nitroglycerin
I was watching a video about Alfred Nobel the other day (shout out Veritasium on YouTube) and got to thinking about how nitroglycerin made the leap from deadly explosive to powerful vasodilator. Looking into this, I was reminded how wild science and medical history is.
Nitroglycerin was discovered in 1847 by Italian chemist Ascanio Sobrero while he was a student at the University of Turin. He prepared the powerful explosive by treating glycerol with a mixture of nitric and sulfuric acids. In 1851, Alfred Nobel, a former student of Sobrero, recognized the potential of nitroglycerin for industrial use. He then went on to invent dynamite as well as several patents for safer handling.
Sobrero first noted the physical effects of nitroglycerin on the body by tasting it, resulting in an instant, violent headache. Yes, tasting the chemicals was a common way to analyze them back in the day. (While it is probably not mentioned as frequently, I had professors in my undergraduate chemistry labs tell us about mouth-pipetting when they were students.) In 1849, Constantin Hering tested nitroglycerin on healthy volunteers. He observed that headaches were caused with ‘such precision’ that it might be used as a homeopathic remedy for headaches.
Around this time, amyl nitrite was being discovered as a powerful vasodilator. Amyl nitrite is chemically similar to nitroglycerin, although it lacks two of the three nitrite groups (NO2) that are present in nitroglycerin. William Murrell first used nitroglycerin for angina (chest pain) in 1876. It is worth noting that nitroglycerin was first registered in the British Pharmacopeia as a treatment for hypertension (high blood pressure). While scientists were able to create a more stable preparation for treatment, little was understood about the underlying mechanism of action until the mid 20th century.
In 1977, Ferid Murad discovered the release of nitric oxide from nitroglycerin and its action on vascular smooth muscle. Robert Furchgott and John Zawadski noted the importance of the endothelium in acetylcholine-induced vasorelaxation in 1980, and in 1987 Louis Ignarro and Salvador Moncada identified nitric oxide as the endothelial-derived relaxing factor. It is now understood that nitroglycerin metabolized to nitric oxide and is a key component of vascular tone in endothelial cells like the ones that line the heart and are key in regulating blood flow, maintaining the vascular barrier, and interacting with heart muscle cells.
While nitroglycerin is less common as an explosive these days, it is still a common cardiovascular medication, mainly due to it’s ability to produce fast-acting results in acute situations.
Sources
Marsh N, Marsh A. A short history of nitroglycerine and nitric oxide in pharmacology and physiology. Clin Exp Pharmacol Physiol. 2000 Apr;27(4):313-9
Steinhorn BS, Loscalzo J, Michel T. Nitroglycerin and Nitric Oxide–A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med. 2015 Jul 16;373(3):277-80.
Montinari MR, Minelli S, Horowitz JD, De Caterina R. Explosive discovery, surprising future: The extraordinary journey of nitroglycerin, nitroderivatives and nitric oxide. Vascul Pharmacol. 2025 Sep;160:107517.