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Role of the Melatonin System in the Control of Sleep

Therapeutic Implications

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Abstract

The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT1 (melatonin la) and MT2 (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals. Both receptors are highly concentrated in the SCN. In diurnal animals, exogenous melatonin induces sleep over a wide range of doses. In healthy humans, melatonin also induces sleep, although its maximum hypnotic effectiveness, as shown by studies of the timing of dose administration, is influenced by the circadian phase.

In both young and elderly individuals with primary insomnia, nocturnal plasma melatonin levels tend to be lower than those in healthy controls. There are data indicating that, in affected individuals, melatonin therapy may be beneficial for ameliorating insomnia symptoms. Melatonin has been successfully used to treat insomnia in children with attention-deficit hyperactivity disorder or autism, as well as in other neurodevelopmental disorders in which sleep disturbance is commonly reported.

In circadian rhythm sleep disorders, such as delayed sleep-phase syndrome, melatonin can significantly advance the phase of the sleep/wake rhythm. Similarly, among shift workers or individuals experiencing jet lag, melatonin is beneficial for promoting adjustment to work schedules and improving sleep quality.

The hypnotic and rhythm-regulating properties of melatonin and its agonists (ramelteon, agomelatine) make them an important addition to the armamentarium of drugs for treating primary and secondary insomnia and circadian rhythm sleep disorders.

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Acknowledgements

The authors would like to acknowledge the comments provided by anonymous reviewers, which considerably improved the paper.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Comprehensive Center for Sleep Medicine, Department of Pulmonary, Critical Care, and Sleep Medicine, Mt Sinai School of Medicine, 1176 - 5th Avenue, 6th Floor, New York, New York, 10029, USA

    Seithikurippu R. Pandi-Perumal

  2. Department of Physiology, School of Medical Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

    Venkatramanujan Srinivasan

  3. Sleep and Alertness Clinic, University Health Network, Toronto, Ontario, Canada

    D. Warren Spence

  4. Departamento de Fisiologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Daniel P. Cardinali

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  1. Seithikurippu R. Pandi-Perumal
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Pandi-Perumal, S.R., Srinivasan, V., Spence, D.W. et al. Role of the Melatonin System in the Control of Sleep. CNS Drugs 21, 995–1018 (2007). https://doi.org/10.2165/00023210-200721120-00004

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