Advances in Therapy

, Volume 26, Issue 6, pp 613-626

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Ramelteon: a review of its therapeutic potential in sleep disorders

  • Seithikurippu R. Pandi-PerumalAffiliated withSomnogen Inc Email author 
  • , Venkatramanujam SrinivasanAffiliated withSri Sathya Sai Medical, Educational and Research Foundation
  • , D. Warren SpenceAffiliated withSleep and Alertness Clinic
  • , Adam MoscovitchAffiliated withCanadian Sleep Institute and CSI Research Center
  • , Rüdiger HardelandAffiliated withInstitute of Zoology and Anthropology, University of Goettingen
  • , Gregory M. BrownAffiliated withDepartment of Psychiatry, Faculty of Medicine, University of Toronto
  • , Daniel P. CardinaliAffiliated withDepartamento de Docencia e Investigación, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina


Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT1 and MT2 melatonin receptors. Ramelteon’s half-life is longer than that of melatonin, being metabolized in the body to four main metabolites, M-I, M-II, M-III, and M-IV. M-II has an affinity to MT1 and MT2 of about one-tenth of the parent compound, but its concentration in the circulation exceeds that of ramelteon by more than an order of magnitude. Ramelteon is effective in decreasing latency to persistent sleep and increasing total sleep time in freely moving monkeys. A number of clinical studies have been undertaken to study the efficacy of ramelteon in subjects with chronic insomnia. In almost all of these studies, ramelteon, in various doses of 4, 8, or 16 mg most commonly, significantly reduced sleep latency and increased sleep duration. Its primary action in sleep promotion is not a generalized gamma-aminobutyric (GABA)-ergic central nervous system depression, but rather it acts as a melatonergic agonist in the suprachiasmatic nucleus (and at other central nervous system sites), from where downstream processes, including GABA-ergic effects, are controlled via the hypothalamic sleep switch. Unlike other commonly prescribed hypnotic drugs, ramelteon is not associated with next morning hangover effects or reductions in alertness, nor has it been shown to cause withdrawal symptoms. The adverse symptoms reported with ramelteon are mild. All long-term investigations that have been carried out support the conclusion that ramelteon is a well tolerated and effective drug for the treatment of insomnia.


hypnotic insomnia melatonin ramelteon