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Melatonin: Difference between revisions
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melatonin is a full agonist of melatonin receptor 1 (picomolar binding affinity) and melatonin receptor 2 (nanomolar binding affinity), both of which belong to the class of G-protein coupled receptors (GPCRs).<ref name=":0">Jockers R, Delagrange P, Dubocovich ML, Markus RP, Renault N, Tosini G, et al. (September 2016). "Update on melatonin receptors: IUPHAR Review 20". ''British Journal of Pharmacology''. '''173''' (18): 2702–25. doi:10.1111/bph.13536. PMC 4995287. <nowiki>PMID 27314810</nowiki>.</ref> Melatonin receptors 1 and 2 are both G<sub>i/o</sub>-coupled GPCRs, although melatonin receptor 1 is also G<sub>q</sub>-coupled.<ref name=":0" /> Melatonin also acts as a high-capacity free radical scavenger within mitochondria which also promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase via signal transduction through melatonin receptors.<ref name=":0" /><br />Melatonin is metabolized in the liver by cytochrome P450 enzyme CYP1A2 to 6-hydroxymelatonin. Metabolites are conjugated with sulfuric acid or glucuronic acid for excretion in the urine. 5% of melatonin is excreted in the urine as the unchanged drug.<ref>Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C (April 2017). "Melatonin: Pharmacology, Functions and Therapeutic Benefits". ''Current Neuropharmacology''. '''15''' (3): 434–443. doi:10.2174/1570159X14666161228122115. PMC 5405617. <nowiki>PMID 28503116</nowiki>.</ref> Some of the metabolites formed via the reaction of melatonin with a free radical include cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), and N1-acetyl-5-methoxykynuramine (AMK).<ref name=":0" /> | melatonin is a full agonist of melatonin receptor 1 (picomolar binding affinity) and melatonin receptor 2 (nanomolar binding affinity), both of which belong to the class of G-protein coupled receptors (GPCRs).<ref name=":0">Jockers R, Delagrange P, Dubocovich ML, Markus RP, Renault N, Tosini G, et al. (September 2016). "Update on melatonin receptors: IUPHAR Review 20". ''British Journal of Pharmacology''. '''173''' (18): 2702–25. doi:10.1111/bph.13536. PMC 4995287. <nowiki>PMID 27314810</nowiki>.</ref> Melatonin receptors 1 and 2 are both G<sub>i/o</sub>-coupled GPCRs, although melatonin receptor 1 is also G<sub>q</sub>-coupled.<ref name=":0" /> Melatonin also acts as a high-capacity free radical scavenger within mitochondria which also promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase via signal transduction through melatonin receptors.<ref name=":0" /><br />Melatonin is metabolized in the liver by cytochrome P450 enzyme CYP1A2 to 6-hydroxymelatonin. Metabolites are conjugated with sulfuric acid or glucuronic acid for excretion in the urine. 5% of melatonin is excreted in the urine as the unchanged drug.<ref>Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C (April 2017). "Melatonin: Pharmacology, Functions and Therapeutic Benefits". ''Current Neuropharmacology''. '''15''' (3): 434–443. doi:10.2174/1570159X14666161228122115. PMC 5405617. <nowiki>PMID 28503116</nowiki>.</ref> Some of the metabolites formed via the reaction of melatonin with a free radical include cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), and N1-acetyl-5-methoxykynuramine (AMK).<ref name=":0" /> | ||
==Subjective effects== | ==Subjective effects== | ||
{{Preamble/SubjectiveEffects}} | {{Preamble/SubjectiveEffects}} | ||
{{effects/base | {{effects/base | ||
|{{effects/physical| | |{{effects/physical| | ||
*'''[[Effect::Sedation]]''' - Melatonin does not produce sedation in the manner of central nervous depressants like [[alcohol]], [[benzodiazepines]], or [[zolpidem]]. | *'''[[Effect::Sedation]]''' - Melatonin does not produce sedation in the manner of central nervous depressants like [[alcohol]], [[benzodiazepines]], or [[zolpidem]]. | ||
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**'''[[Effect::Physical euphoria]]''' - This effect can occur alongside [[Muscle relaxation]], and is only present at heavy dosages when the user resists the urge to sleep. | **'''[[Effect::Physical euphoria]]''' - This effect can occur alongside [[Muscle relaxation]], and is only present at heavy dosages when the user resists the urge to sleep. | ||
*'''[[Effect::Decreased libido]]''' - This effect can be caused by the [[Sedation]] or by the fact that melatonin can inhibit secretion of hormones that control sexual functions.{{citation needed}} | *'''[[Effect::Decreased libido]]''' - This effect can be caused by the [[Sedation]] or by the fact that melatonin can inhibit secretion of hormones that control sexual functions.{{citation needed}} | ||
}} | }} | ||
|{{effects/cognitive| | |{{effects/cognitive| | ||
*'''[[Effect::Sleepiness]]''' - Regarding its effects on the user's physical energy levels, melatonin is commonly considered to facilitate sleepiness. It is often used and sold as a sleep aid and mimics one's natural circadian cycle. | *'''[[Effect::Sleepiness]]''' - Regarding its effects on the user's physical energy levels, melatonin is commonly considered to facilitate sleepiness. It is often used and sold as a sleep aid and mimics one's natural circadian cycle. | ||
*'''[[Effect::Anxiety Suppression or Anxiety]]''' - Although this substance decreases anxiety with most people, it can also cause anxiety by some. | |||
*'''[[Effect::Anxiety Suppression or Anxiety]''' - Although this substance decreases anxiety with most people, it can also cause anxiety by some. | |||
*'''[[Effect::Dream potentiation]]''' - Melatonin is extremely effective at increasing the duration, occurrence, and vividness of dreams. It is very common for people to note that their dreams had noticeably increased the morning after ingesting melatonin as a sleep aid. Melatonin is sometimes used to increase the chances of lucid dreaming. | *'''[[Effect::Dream potentiation]]''' - Melatonin is extremely effective at increasing the duration, occurrence, and vividness of dreams. It is very common for people to note that their dreams had noticeably increased the morning after ingesting melatonin as a sleep aid. Melatonin is sometimes used to increase the chances of lucid dreaming. | ||
*'''[[Effect::Depersonalization]]''' - Depersonalization can present itself upon the come-up and persist well into the next day if the user has ingested a massive dose. | *'''[[Effect::Depersonalization]]''' - Depersonalization can present itself upon the come-up and persist well into the next day if the user has ingested a massive dose. | ||
*'''[[Effect::Irritability]]''' Irritability is only present at high dosages when the user resists the urge to sleep. | *'''[[Effect::Irritability]]''' Irritability is only present at high dosages when the user resists the urge to sleep. | ||
}} | }} | ||
{{effects/aftereffects| | {{effects/aftereffects| | ||
*'''[[Effect::Headaches]]''' - A small subset of people may experience headaches the day after ingesting melatonin.<ref>Melatonin Side Effects (EverydayHealth) | http://www.everydayhealth.com/drugs/melatonin</ref> | *'''[[Effect::Headaches]]''' - A small subset of people may experience headaches the day after ingesting melatonin.<ref>Melatonin Side Effects (EverydayHealth) | http://www.everydayhealth.com/drugs/melatonin</ref> | ||
*'''[[Effect::Sleepiness]]''' | *'''[[Effect::Sleepiness]]''' | ||
}} | |||
}} | }} | ||