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CNS Drugs

, Volume 21, Issue 12, pp 995–1018 | Cite as

Role of the Melatonin System in the Control of Sleep

Therapeutic Implications
  • Seithikurippu R. Pandi-Perumal
  • Venkatramanujan Srinivasan
  • D. Warren Spence
  • Daniel P. Cardinali
Review Article

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.

Keywords

Melatonin Sleep Onset Melatonin Receptor Agomelatine Melatonin Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Seithikurippu R. Pandi-Perumal
    • 1
  • Venkatramanujan Srinivasan
    • 2
  • D. Warren Spence
    • 3
  • Daniel P. Cardinali
    • 4
  1. 1.Comprehensive Center for Sleep Medicine, Department of Pulmonary, Critical Care, and Sleep MedicineMt Sinai School of MedicineNew YorkUSA
  2. 2.Department of Physiology, School of Medical SciencesUniversity Sains MalaysiaKubang Kerian, KelantanMalaysia
  3. 3.Sleep and Alertness ClinicUniversity Health NetworkTorontoCanada
  4. 4.Departamento de Fisiologia, Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

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