title: Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders.
abstract: Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non-24-hour sleep-wake disorder (or non-24). However, three additional commercially available melatonin receptor agonists-agomelatine, prolonged-release melatonin, and ramelteon-have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs.
authors: Department of Medical Affairs, Vanda Pharmaceuticals, Inc., Washington, D.C.. Trey.Williams@vandapharma.com.
authors: Wilbur P Trey
authors: WP
authors: Williams
authors: Department of Medical Affairs, Vanda Pharmaceuticals, Inc., Washington, D.C.
authors: Dewey E
authors: DE
authors: McLin
authors: Department of Clinical Development, Vanda Pharmaceuticals, Inc., Washington, D.C.
authors: Marlene A
authors: MA
authors: Dressman
authors: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: David N
authors: DN
authors: Neubauer
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001572:Benzofurans / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000187:drug effects*; D003521:Cyclopropanes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019587:Dietary Supplements; D006801:Humans; D044094:Receptors, Melatonin / Q000819:agonists*; D012893:Sleep Wake Disorders / Q000145:classification / Q000188:drug therapy*; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D001572:Benzofurans; D003521:Cyclopropanes; D044094:Receptors, Melatonin; C084711:agomelatine; D009281:Naphthalenes; C478745:tasimelteon
keywords: circadian rhythm; drug effects; melatonin agonists; sleep drug effects