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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587134/ https://www.ncbi.nlm.nih.gov/pubmed/34770988 http://dx.doi.org/10.3390/molecules26216581 |
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author | Pearson, Russell Butler, Anthony |
author_facet | Pearson, Russell Butler, Anthony |
author_sort | Pearson, Russell |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8587134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85871342021-11-13 Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance Pearson, Russell Butler, Anthony Molecules Review 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. MDPI 2021-10-30 /pmc/articles/PMC8587134/ /pubmed/34770988 http://dx.doi.org/10.3390/molecules26216581 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Pearson, Russell Butler, Anthony Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance |
title | 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_short | Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance |
title_sort | glyceryl trinitrate: history, mystery, and alcohol intolerance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587134/ https://www.ncbi.nlm.nih.gov/pubmed/34770988 http://dx.doi.org/10.3390/molecules26216581 |
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