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Melatonin and Melatonergic Drugs in Clinical Practice pp 205–219Cite as

Melatonin: An Introduction to Its Physiological and Pharmacological Effects in Humans

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Abstract

Melatonin is a methoxyindole that, under normal environmental conditions, is synthesized and secreted principally by the pineal gland at night. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production depending on the light schedule. The nycthemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin levels or urine levels of 6-sulphatoxymelatonin, the main hepatic metabolite.

Secretion of melatonin adjusts to night length, and its primary physiological function is to convey information concerning the daily cycle of light and darkness to body structures. This information is used for the organization of functions that respond to changes in the photoperiod, such as seasonal rhythms. However, in temperate areas under field conditions, there is only limited evidence for a relationship between seasonal rhythmicity of physiological functions in humans and possible alterations in the melatonin message. In addition, daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organization of circadian rhythms. Although the evidence for possible functions of this hormone in humans is mainly based on correlative observations between physiological effects and changes in melatonin secretion, there is some evidence that melatonin stabilizes and strengthens the coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organization of other physiological functions, such as immune and antioxidant defenses, hemostasis, and glucose regulation, also depends on the melatonin signal.

The difference between the physiological and pharmacological effects of melatonin is not always clear, but is based upon the dose, and not the duration, of the hormone message. A pharmacological dose provides supraphysiological levels of melatonin, while a “physiological” dose provides plasma levels of the same order of magnitude as a nocturnal peak. However, when a low melatonin dose is given using a simple capsule, a narrow hormone signal is achieved, which does not mimic endogenous secretion. It is admitted that a “physiological” dose provides plasma melatonin levels of the same order of magnitude as a nocturnal peak. Since the regulatory system of melatonin secretion is complex, involving central and autonomic pathways, there are many pathophysiological situations in which melatonin secretion can be disturbed. The resulting change could increase predisposition to a disease, add to the severity of symptoms, or modify the course and outcome of the disorder. Since melatonin receptors are very widely distributed in the body, putative therapeutic indications of this compound are multiple. Great advances in therapeutics could be made by performing multicenter trials in large series of patients in order to establish the efficacy of melatonin and the absence of long-term toxicity.

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Authors and Affiliations

  1. Hormone Laboratory, Hospices Civils de Lyon, 59 Bd Pinel, Bron, 69677, France

    Bruno Claustrat PhD

  2. INSERM, U846 Chronobiology Group, Hospices Civils de Lyon, 59 bd Pinel, 18 Avenue du Doyen Lépine, Bron, 69500, France

    Bruno Claustrat PhD

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Editors and Affiliations

  1. Sri Sathya Sai Medical Educational and Research Foundation, An International Medical Sciences Research Center, Coimbatore, Tamil Nadu, India

    V. Srinivasan

  2. Department of Obstetrics and Gynecology, Hadassah Hebrew-University Medical Center, Jerusalem, Israel

    Amnon Brzezinski

  3. Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey

    Sukru Oter

  4. Department of Psychiatry Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA

    Samuel D. Shillcutt

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Claustrat, B. (2014). Melatonin: An Introduction to Its Physiological and Pharmacological Effects in Humans. In: Srinivasan, V., Brzezinski, A., Oter, S., Shillcutt, S. (eds) Melatonin and Melatonergic Drugs in Clinical Practice. Springer, New Delhi. https://doi.org/10.1007/978-81-322-0825-9_14

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