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Paper
Title

Melatonergic Treatment: Focus on Metabolism andChronobiology

Year: 1395
COI: JR_FOCS-2-1_005
Language: EnglishView: 238
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Authors

Rüdiger Hardeland - Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University ofGöttingen, Göttingen, Germany

Abstract:

Introduction: Melatonin is produced in various organs, but its preferentially nocturnalsynthesis and release by the pineal gland is decisive for its chronobiological actions.The short half-life of circulating melatonin has been reason for developing syntheticmelatonergic agonists. With regard to age- and disease-related dysfunction of themelatonergic system, treatment with melatonin or its synthetic analogs may be used foralleviating health problems with a respective etiology. This review addresses limitationsarising from drug-specific metabolism and disregarded chronobiological rules.Metabolism: Differences are illustrated by comparing the metabolism of melatonin andtwo approved synthetic melatonergic agonists, ramelteon and agomelatine. Apart fromhydroxylation and dealkylation reactions, melatonin can be converted to methoxylatedkynuramines, a route absent in the two synthetic drugs. An unsual property is present inthe ramelteon metabolite M-II, which still displays melatonergic activity, but attains 30 to100 times higher levels than the parent compound. Two double-hydroxylated agomelatinemetabolites may be involved in sometimes occurring hepatotoxicity.Chronobiology of Melatonergic Drugs: Sleep latency facilitation and readjustmentof circadian rhythms require only short actions. Circadian entrainment must considerthe phase response curve and requires repetitive well-timed administration. Findingsin nocturnally active rodents cannot be generally translated to humans, especially notregarding sleep and, perhaps, not in insulin resistance.Conclusions: Melatonin and synthetic analogs can be suitable for treating sleep-onsetdifficulties, circadian rhythm sleep disorders and subtypes of depression with an etiologyof circadian dysfunction. Applications in the field of metabolic syndrome and insulinresistance have to be seen with caution

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This Paper COI Code is JR_FOCS-2-1_005. Also You can use the following address to link to this article. This link is permanent and is used as an article registration confirmation in the Civilica reference:

https://civilica.com/doc/515188/

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Hardeland, Rüdiger,1395,Melatonergic Treatment: Focus on Metabolism andChronobiology,https://civilica.com/doc/515188

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