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Summary
Bachmann A et al.  
Melatonin

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2015; 12 (4): 342-352

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Keywords: antioxidantchronobiologycircadian rhythmCNSjetlagMelatoninsleepsleep disorder

Chemistry: Melatonin is an indolamine which accrues via serotonin from the amino acid L tryptophan. Point of origin: The main point of origin in humans is the epiphysis.
Physiological relevance: – In animals: Due to lighting condition influenced chronobiological processes, melatonin has impact on reproduction and growth. In consequence of its anti-oxidative efficacy, melatonin has protective effects from environmental influences. – In humans: Melatonin can be found in a variety of cells like in lymphocytes and bone marrow cells, the thymus gland and in the gastrointestinal tract as well as in the skin and in the eyes.
There, it exerts numerous paracrine functions. The effects of melatonin in humans are divers and not fully understood yet. Melatonin results in down-regulation of several biological and oxidative processes. It plays a role in the endogenous rhythm formation, is a potent anti-oxidant and has immunomodulatory effects. Of clinical relevance is a potential correlation with the development of breast cancer.
Pharmacotherapy: The field of research and the clinical relevance of chronobiology and the possible indications for the use of melatonin is broad. However, there are not sufficient data on the efficacy and safety of melatonin from clinical trials. Melatonin is used in retarded formulation and is approved for the treatment of sleep disorders in people > 55 years of age with disorders in the sleep architecture.
In contrast to benzodiazepines, which are commonly used for the treatment of insomnia, it appears that melatonin does not result in an impairment of psycho-motorics on the following day. The subjective perception of the quality of sleep and the mental performance are improved on the next morning. However, the difference in the response rate compared to placebo is low and therefore melatonin can be considered a weak hypnotic agent only. The rate of recurrent insomnia can not be estimated from the current studies available due to the low numbers of patients.
Melatonin is a weak hypnotic which is approved for the treatment of sleep disorders in people > 55 years of age with disorders in the sleep architecture. It is also used for the treatment of sleep disorders in children as well as in adults with neurological diseases like abnormal development of the CNS and impaired vision, cerebral palsy, attention deficit disorder and autism. A melatonin receptor antagonist is also approved for the treatment of depression. There are inconclusive data regarding the efficacy of melatonin in the treatment of subjective afflictions from jetlag symptoms.
Compounds: – Oral agents: Melatonin is sold over the counter as food supplement in Canada and the U.S. According to the German Drug Act, melatonin is available on prescription only. This is also the case for any melatonin-containing drugs, independent of the concentrations contained. Circadin®: In 2007 Circadin® received approval from the European Commission for the treatment of sleep disorders in people > 55 years of age. It received marketing approval in Switzerland in 2009 and is traded since 2010. Circadin® contains 2 mg melatonin in retarded formulation. The recommended dosage is 2 mg melatonin, taken 1–2 hours before going to bed after the last meal for at least 3 weeks. Capsules containing up to 5 mg melatonin with varying additives are available from different manufacturers on the European market for supplemental diets. Agomelatin®: is a substance with a chemical structure comparable to melatonin. In contrast to melatonin, which has affinity to melatonin receptors types MT1 and MT2, Agomelatin® has antagonistic characteristics on the serotonin receptor 5-HT2c. Agomelatin® has marketing approval for the treatment of depression. – Topical agents: Melatonin is used as hair restorer: Trichosense® Drug safety: Short term melatonin intake (< 3 months) in low doses should not have any deleterious effects in adults. A final conclusion on the safety of long term intake of melatonin cannot be drawn due to lack of data.
 
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