Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies
Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT<sub>1</sub> and MT<sub>2</sub> and are unsuitable for chr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Diseases |
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| Online Access: | https://www.mdpi.com/2079-9721/9/1/18 |
| _version_ | 1827698157247528960 |
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| author | Rüdiger Hardeland |
| author_facet | Rüdiger Hardeland |
| author_sort | Rüdiger Hardeland |
| collection | DOAJ |
| description | Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT<sub>1</sub> and MT<sub>2</sub> and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin’s tissue levels, its formation in mitochondria, and detoxification of free radicals. |
| first_indexed | 2024-03-10T13:24:34Z |
| format | Article |
| id | doaj.art-c77c9c9d914c4d87b624c33e9881650a |
| institution | Directory Open Access Journal |
| issn | 2079-9721 |
| language | English |
| last_indexed | 2024-03-10T13:24:34Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diseases |
| spelling | doaj.art-c77c9c9d914c4d87b624c33e9881650a2023-11-21T09:48:36ZengMDPI AGDiseases2079-97212021-03-01911810.3390/diseases9010018Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin TherapiesRüdiger Hardeland0Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, 37073 Göttingen, GermanyMelatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT<sub>1</sub> and MT<sub>2</sub> and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin’s tissue levels, its formation in mitochondria, and detoxification of free radicals.https://www.mdpi.com/2079-9721/9/1/18circadianentrainmentinflammationmelatoninmitochondriareceptor saturation |
| spellingShingle | Rüdiger Hardeland Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies Diseases circadian entrainment inflammation melatonin mitochondria receptor saturation |
| title | Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies |
| title_full | Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies |
| title_fullStr | Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies |
| title_full_unstemmed | Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies |
| title_short | Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies |
| title_sort | divergent importance of chronobiological considerations in high and low dose melatonin therapies |
| topic | circadian entrainment inflammation melatonin mitochondria receptor saturation |
| url | https://www.mdpi.com/2079-9721/9/1/18 |
| work_keys_str_mv | AT rudigerhardeland divergentimportanceofchronobiologicalconsiderationsinhighandlowdosemelatonintherapies |