Nitroglycerin’s explosive beginnings

Clinical
By
Phoebe Armstrong
-

Nitroglycerin has had an eventful career. Best known today as a treatment for angina, it had made a name for itself in the explosives industry.

In 1847, Italian chemist Ascanio Sobrero synthesised glyceryl trinitrate. When he placed a small amount on his tongue, he developed a severe, throbbing headache that lasted for hours. Sobrero was concerned by the compound’s volatile nature and did not see any obvious practical use for it.1

That changed when Alfred Nobel combined it with an inert absorbent material to create dynamite,1 giving nitroglycerin a practical use as an explosive. Meanwhile, physicians were noticing that related nitrate compounds had powerful effects on blood vessels. One of the earliest clues came from amyl nitrite. In 1859, English chemist Frederick Guthrie observed that inhaling it caused flushing, a racing pulse and visibly throbbing arteries.2

Scottish physician T. Lauder Brunton later tested whether these effects could help people with angina, reporting in 1867 that inhaled amyl nitrite could relieve severe chest pain within seconds – lowering blood pressure and reducing the heart’s workload.2 Before long, attention turned to nitroglycerin itself.

In 1879, physician William Murrell tested it on himself. After taking a diluted solution, he experienced a rapid pulse, a drop in blood pressure and a severe headache.3 He nevertheless began using small doses in patients with angina, and found their chest pain could ease within minutes.3,4

From angina to wider clinical use

For decades, nitroglycerin’s effects were put down to opening up the coronary arteries.5 Later research showed it’s more nuanced. Nitroglycerin is a powerful venodilator.6 By widening the veins, it lets blood pool peripherally, reducing the amount returning to the heart.6 This lowers ventricular filling pressure and wall tension and, in turn, reduces the heart’s oxygen requirements.5,7

That mechanism made it versatile. Sublingual tablets and sprays gave rapid relief for acute angina attacks,8 while ointments and transdermal patches, developed in the 1970s and 1980s, offered sustained relief for stable angina.9,10

In hospitals, intravenous nitroglycerin eased cardiac workload in acute heart failure and myocardial infarction.6,11 And its smooth-muscle-relaxing effect found use in treating ischaemic digital ulcers.6,12

A problem with continuous use

However, continuous use had a catch: its effectiveness could wane. This was already noticed among workers exposed to nitroglycerin while manufacturing explosives. Some developed severe headaches upon returning to work after a break.1 In patients with prolonged exposure, blood vessels became less responsive, and the drug’s effects diminished.9 This led to a nitrate-free period being built into treatment, usually 8–12 hours each day,9 limiting tolerance.

But there was another piece of the puzzle to solve: how did nitroglycerin cause blood vessels to relax? Research in the late twentieth century established that organic nitrates act as sources of nitric oxide (NO),1 which serves as a signalling molecule involved in smooth muscle cell relaxation and other cardiovascular effects.6 This work helped earn the 1998 Nobel Prize in Physiology or Medicine – awarded to Robert Furchgott, Louis Ignarro and Ferid Murad.1

Where nitroglycerin fits in today

Nitroglycerin remains an important cardiovascular drug, but its uses are now more clearly defined. Sublingual tablets and sprays continue to be used for rapid relief of anginal symptoms.8 Intravenous nitroglycerin still has a role in treating severe acute heart failure, particularly in patients with hypertension.13

But some assumptions of the drug have changed. Relief of chest pain after taking nitroglycerin was once treated as evidence that the pain was cardiac.15 Nitroglycerin can relax smooth muscle elsewhere including the oesophagus, so symptom relief does not reliably distinguish coronary disease from other causes of chest pain.14,15

There is also continuing debate about the benefits of intravenous nitrates in acute heart failure, with evidence reviews finding uncertainty around outcomes.7,16

Nitroglycerin’s most lasting contribution may be less about the drug itself than what it revealed about the body. Understanding its relationship with nitric oxide opened up a much broader field of cardiovascular research, including the development of treatments targeting the nitric oxide signalling pathway.1

A compound that began as an unstable explosive became a tool for understanding how the body regulates blood vessels. And, more than 170 years after Sobrero first made it, nitroglycerin remains part of everyday cardiovascular medicine.

References

  1. Montinari MR, Minelli S, Horowitz JD, De Caterina R. Explosive discovery, surprising future: the extraordinary journey of nitroglycerin, nitroderivatives and nitric oxide. Vasc Pharmacol. 2025;107517.
  2. Brunton TL. On the use of nitrite of amyl in angina pectoris. Lancet. 1867;90(2291):97-98.
  3. Murrell W. Nitro-glycerine as a remedy for angina pectoris. Lancet. 1879;113(2891):113-115.
  4. Murrell W. Nitro-glycerine as a remedy for angina pectoris. London: T. Richards; 1880.
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  6. Kim KH, Adnan G, Schaller DJ. Nitroglycerin. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026.
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  8. Parker JO, Vankoughnett KA, Farrell B. Nitroglycerin lingual spray: clinical efficacy and dose-response relation. Am J Cardiol. 1986;57(1):1-5.
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  11. Flaherty JT, Becker LC, Bulkley BH, Weiss JL, Gerstenblith G, Kallman CH, et al. A randomized prospective trial of intravenous nitroglycerin in patients with acute myocardial infarction. Circulation. 1983;68(3):576-588.
  12. Wheeland RG, Gilchrist RW Jr, Young CJ Jr. Treatment of ischemic digital ulcers with nitroglycerin ointment. J Dermatol Surg Oncol. 1983;9(7):548-551.
  13. Levy P, Compton S, Welch R, Delgado G, Jennett A, Penugonda N, et al. Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis. Ann Emerg Med. 2007;50(2):144-152.
  14. Grailey K, Glasziou PP. Diagnostic accuracy of nitroglycerine as a ‘test of treatment’ for cardiac chest pain: a systematic review. Emerg Med J. 2012;29(3):173-176.
  15. Henrikson CA, Howell EE, Bush DE, Miles JS, Meininger GR, Friedlander T, et al. Chest pain relief by nitroglycerin does not predict active coronary artery disease. Ann Intern Med. 2003;139(12):979-986.
  16. Wakai A, McCabe A, Kidney R, Brooks SC, Seupaul RA, Diercks DB, et al. Nitrates for acute heart failure syndromes. Cochrane Database Syst Rev. 2013;(8):CD005151.