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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/21/6581 |
| _version_ | 1797511975493697536 |
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| author | Russell Pearson Anthony Butler |
| author_facet | Russell Pearson Anthony Butler |
| author_sort | Russell Pearson |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:55:31Z |
| format | Article |
| id | doaj.art-16ad30072ab648eaa668366f55e2e575 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:55:31Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-16ad30072ab648eaa668366f55e2e5752023-11-22T21:23:26ZengMDPI AGMolecules1420-30492021-10-012621658110.3390/molecules26216581Glyceryl Trinitrate: History, Mystery, and Alcohol IntoleranceRussell Pearson0Anthony Butler1School of Pharmacy & Bioengineering, Keele University, Newcastle-under-Lyme ST5 5BG, Staffordshire, UKSchool of Psychology & Neuroscience, University of St Andrews, St Andrews KY16 9JP, UKGlyceryl 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.https://www.mdpi.com/1420-3049/26/21/6581glyceryl trinitrateNO-donorsorganic nitratesnitric oxidealdehyde dehydrogenasenitrate tolerance |
| spellingShingle | Russell Pearson Anthony Butler Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance Molecules glyceryl trinitrate NO-donors organic nitrates nitric oxide aldehyde dehydrogenase nitrate tolerance |
| 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 | glyceryl trinitrate NO-donors organic nitrates nitric oxide aldehyde dehydrogenase nitrate tolerance |
| url | https://www.mdpi.com/1420-3049/26/21/6581 |
| work_keys_str_mv | AT russellpearson glyceryltrinitratehistorymysteryandalcoholintolerance AT anthonybutler glyceryltrinitratehistorymysteryandalcoholintolerance |