Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance

Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit...

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Autores principales:	Russell Pearson, Anthony Butler
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glyceryl trinitrate NO-donors organic nitrates nitric oxide aldehyde dehydrogenase nitrate tolerance Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/16ad30072ab648eaa668366f55e2e575
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spelling	oai:doaj.org-article:16ad30072ab648eaa668366f55e2e5752021-11-11T18:33:33ZGlyceryl Trinitrate: History, Mystery, and Alcohol Intolerance10.3390/molecules262165811420-3049https://doaj.org/article/16ad30072ab648eaa668366f55e2e5752021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6581https://doaj.org/toc/1420-3049Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN’s bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.Russell PearsonAnthony ButlerMDPI AGarticleglyceryl trinitrateNO-donorsorganic nitratesnitric oxidealdehyde dehydrogenasenitrate toleranceOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6581, p 6581 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glyceryl trinitrate NO-donors organic nitrates nitric oxide aldehyde dehydrogenase nitrate tolerance Organic chemistry QD241-441
spellingShingle	glyceryl trinitrate NO-donors organic nitrates nitric oxide aldehyde dehydrogenase nitrate tolerance Organic chemistry QD241-441 Russell Pearson Anthony Butler Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
description	Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN’s bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.
format	article
author	Russell Pearson Anthony Butler
author_facet	Russell Pearson Anthony Butler
author_sort	Russell Pearson
title	Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
title_short	Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
title_full	Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
title_fullStr	Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
title_full_unstemmed	Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance
title_sort	glyceryl trinitrate: history, mystery, and alcohol intolerance
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/16ad30072ab648eaa668366f55e2e575
work_keys_str_mv	AT russellpearson glyceryltrinitratehistorymysteryandalcoholintolerance AT anthonybutler glyceryltrinitratehistorymysteryandalcoholintolerance
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Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance

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