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Review Article| Volume 4, ISSUE 2, P179-193, June 2009

Melatonin and Melatonin Analogues

  • Shantha M.W. Rajaratnam
    Correspondence
    Corresponding author. School of Psychology, Psychiatry and Psychological Medicine, Monash University, Building 17, Clayton, Victoria 3800, Australia.
    Affiliations
    School of Psychology, Psychiatry and Psychological Medicine, Monash University, Building 17, Clayton, Victoria 3800, Australia

    Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA

    Division of Sleep Medicine, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA
    Search for articles by this author
  • Daniel A. Cohen
    Affiliations
    Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA

    Harvard Medical School, 25 Shattuck Street, Boston, MA 02215, USA

    Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, KS 450, Boston, MA 02215, USA
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  • Naomi L. Rogers
    Affiliations
    Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Building F, Level 5, Camperdown NSW 2050, Australia
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      Keywords

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      References

        • Arendt J.
        • Rajaratnam S.M.
        Melatonin and its agonists: an update.
        Br J Psychiatry. 2008; 193: 267-269
        • Redman J.
        • Armstrong S.
        • Ng K.T.
        Free-running activity rhythms in the rat: entrainment by melatonin.
        Science. 1983; 219: 1089-1091
        • Arendt J.
        • Bojkowski C.
        • Folkard S.
        • et al.
        Some effects of melatonin and the control of its secretion in humans.
        Ciba Found Symp. 1985; 117: 266-283
        • Perreau-Lenz S.
        • Kalsbeek A.
        • Garidou M.L.
        • et al.
        Suprachiasmatic control of melatonin synthesis in rats: inhibitory and stimulatory mechanisms.
        Eur J Neurosci. 2003; 17: 221-228
        • Perreau-Lenz S.
        • Kalsbeek A.
        • Pevet P.
        • et al.
        Glutamatergic clock output stimulates melatonin synthesis at night.
        Eur J Neurosci. 2004; 19: 318-324
        • Reppert S.M.
        • Perlow M.J.
        • Ungerleider L.G.
        • et al.
        Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey.
        J Neurosci. 1981; 1: 1414-1425
        • Klein D.C.
        • Moore R.Y.
        Pineal N-acetyltransferase and hydroxyindole-O-methyltransferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus.
        Brain Res. 1979; 174: 245-262
        • Pandi-Perumal S.R.
        • Trakht I.
        • Srinivasan V.
        • et al.
        Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways.
        Prog Neurobiol. 2008; 85: 335-353
        • Cassone V.M.
        • Chesworth M.J.
        • Armstrong S.M.
        Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei.
        Physiol Behav. 1986; 36: 1111-1121
        • Sumova A.
        • Illnerova H.
        Melatonin instantaneously resets intrinsic circadian rhythmicity in the rat suprachiasmatic nucleus.
        Neurosci Lett. 1996; 218: 181-184
        • Cassone V.M.
        • Roberts M.H.
        • Moore R.Y.
        Effects of melatonin on 2-deoxy-[1-14C] glucose uptake within rat suprachiasmatic nucleus.
        Am J Phys. 1988; 255: R332-R337
        • von Gall C.
        • Duffield G.E.
        • Hastings M.H.
        • et al.
        CREB in the mouse SCN: a molecular interface coding the phase-adjusting stimuli light, glutamate, PACAP, and melatonin for clockwork access.
        J Neurosci. 1998; 18: 10389-10397
        • Kopp M.
        • Meissl H.
        • Korf H.W.
        The pituitary adenylate cyclase-activating polypeptide-induced phosphorylation of the transcription factor CREB (cAMP response element binding protein) in the rat suprachiasmatic nucleus is inhibited by melatonin.
        Neurosci Lett. 1997; 227: 145-148
        • Reppert S.M.
        • Weaver D.R.
        • Godson C.
        Melatonin receptors step into the light: cloning and classification of subtypes.
        Trends Pharmacol Sci. 1996; 17: 100-102
        • Liu C.
        • Weaver D.R.
        • Jin X.
        • et al.
        Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock.
        Neuron. 1997; 19: 91-102
        • Hunt A.E.
        • Al-Ghoul W.M.
        • Gillette M.U.
        • et al.
        Activation of MT(2) melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock.
        Am J Physiol Cell Physiol. 2001; 280: C110-C118
        • Dubocovich M.L.
        • Yun K.
        • Alghoul W.M.
        • et al.
        Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms.
        FASEB J. 1998; 12: 1211-1220
        • Dubocovich M.L.
        • Hudson R.L.
        • Sumaya I.C.
        • et al.
        Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of circadian rhythms in the C57BL/6 mouse.
        J Pineal Res. 2005; 39: 113-120
        • von Gall C.
        • Weaver D.R.
        • Kock M.
        • et al.
        Melatonin limits transcriptional impact of phosphoCREB in the mouse SCN via the Mel1a receptor.
        Neuroreport. 2000; 11: 1803-1807
        • Dubocovich M.L.
        Melatonin receptors: role on sleep and circadian rhythm regulation.
        Sleep Med. 2007; 8: 34-42
        • Shibata S.
        • Cassone V.M.
        • Moore R.Y.
        Effects of melatonin on neuronal activity in the rat suprachiasmatic nucleus in vitro.
        Neurosci Lett. 1989; 97: 140-144
        • Jin X.
        • von Gall C.
        • Pieschl R.L.
        • et al.
        Targeted disruption of the mouse Mel(1b) melatonin receptor.
        Mol Cell Biol. 2003; 23: 1054-1060
        • Lieberman H.R.
        • Waldhauser F.
        • Garfield G.
        • et al.
        Effects of melatonin on human mood and performance.
        Brain Res. 1984; 323: 201-207
        • Rogers N.L.
        • Dinges D.F.
        • Kennaway D.J.
        • et al.
        Potential action of melatonin in insomnia.
        Sleep. 2003; 26: 1058-1059
        • Hughes R.J.
        • Sack R.L.
        • Lewy A.J.
        The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement.
        Sleep. 1998; 21: 52-68
        • Deacon S.
        • Arendt J.
        Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans.
        Brain Res. 1995; 688: 77-85
        • Dollins A.B.
        • Zhdanova I.V.
        • Wurtman R.J.
        • et al.
        Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.
        Proc Natl Acad Sci U S A. 1994; 91: 1824-1828
        • Buscemi N.
        • Vandermeer B.
        • Hooton N.
        • et al.
        Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis.
        BMJ. 2006; 332: 385-393
        • Herxheimer A.
        • Petrie K.J.
        Melatonin for the prevention and treatment of jet lag (Cochrane Review).
        Cochrane Database Syst Rev. 2002; (CD001520)
        • Buscemi N.
        • Vandermeer B.
        • Hooton N.
        • et al.
        The efficacy and safety of exogenous melatonin for primary sleep disorders: a meta-analysis.
        J Gen Intern Med. 2005; 20: 1151-1158
        • Aldhous M.
        • Franey C.
        • Wright J.
        • et al.
        Plasma concentrations of melatonin in man following oral absorption of different preparations.
        Br J Clin Pharmacol. 1985; 19: 517-521
        • Waldhauser F.
        • Waldhauser M.
        • Lieberman H.R.
        • et al.
        Bioavailability of oral melatonin in humans.
        Neuroendocrinology. 1984; 39: 307-313
        • Redman J.R.
        Circadian entrainment and phase shifting in mammals with melatonin.
        J Biol Rhythms. 1997; 12: 581-587
        • McArthur A.J.
        • Hunt A.E.
        • Gillette M.U.
        Melatonin and signal transduction in the rat suprachiasmatic circadian clock: activation of protein kinase C at dawn and dusk.
        Endocrinology. 1997; 138: 627-634
        • Arendt J.
        • Middleton B.
        • Stone B.
        • et al.
        Complex effects of melatonin: evidence for photoperiodic responses in humans?.
        Sleep. 1999; 22: 625-635
        • Burgess H.J.
        • Revell V.L.
        • Eastman C.I.
        A three pulse phase response curve to three milligrams of melatonin in humans.
        J Physiol. 2008; 586: 639-647
        • Lewy A.J.
        • Bauer V.K.
        • Ahmed S.
        • et al.
        The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light.
        Chronobiol Int. 1998; 15: 71-83
        • Zaidan R.
        • Geoffriau M.
        • Brun J.
        • et al.
        Melatonin is able to influence its secretion in humans: description of a phase response curve.
        Neuroendocrinology. 1994; 60: 105-112
        • Wirz-Justice A.
        • Werth E.
        • Renz C.
        • et al.
        No evidence for a phase delay in human circadian rhythms after a single morning melatonin administration.
        J Pineal Res. 2002; 32: 1-5
        • Sack R.L.
        • Lewy A.J.
        • Hoban T.M.
        Free-running melatonin rhythms in blind people: phase shifts with melatonin and triazolam administration.
        in: Rensing L. van der Heiden U. Mackey M.C. Temporal disorder in human oscillatory systems. Springer-Verlag, Heidelberg1987: 219-224
        • Deacon S.
        • English J.
        • Arendt J.
        Acute phase-shifting effects of melatonin associated with suppression of core body temperature in humans.
        Neurosci Lett. 1994; 178: 32-34
        • Attenburrow M.E.J.
        • Dowling B.A.
        • Sargent P.A.
        • et al.
        Melatonin phase advances circadian rhythm.
        Psychopharmacology (Berl). 1995; 121: 503-505
        • Krauchi K.
        • Cajochen C.
        • Mori D.
        • et al.
        Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature.
        Am J Phys. 1997; 272: R1178-R1188
        • Sharkey K.M.
        • Eastman C.I.
        Melatonin phase shifts human circadian rhythms in a placebo-controlled simulated night-work study.
        Am J Physiol Regul Integr Comp Physiol. 2002; 282: R454-R463
        • Rajaratnam S.M.
        • Dijk D.J.
        • Middleton B.
        • et al.
        Melatonin phase shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones.
        J Clin Endocrinol Metab. 2003; 88: 4303-4309
        • Vandewalle G.
        • Middleton B.
        • Rajaratnam S.M.
        • et al.
        Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiod.
        J Sleep Res. 2007; 16: 148-155
        • Rajaratnam S.M.
        • Middleton B.
        • Stone B.M.
        • et al.
        Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans.
        J Physiol. 2004; 561: 339-351
        • Lockley S.W.
        • Skene D.J.
        • James K.
        • et al.
        Melatonin administration can entrain the free-running circadian system of blind subjects.
        J Endocrinol. 2000; 164: R1-R6
        • Sack R.L.
        • Brandes R.W.
        • Kendall A.R.
        • et al.
        Entrainment of free-running circadian rhythms by melatonin in blind people.
        N Engl J Med. 2000; 343: 1070-1077
        • Lewy A.J.
        • Emens J.S.
        • Sack R.L.
        • et al.
        Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period.
        Chronobiol Int. 2002; 19: 649-658
        • Hack L.M.
        • Lockley S.W.
        • Arendt J.
        • et al.
        The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects.
        J Biol Rhythms. 2003; 18: 420-429
        • Lewy A.J.
        • Emens J.S.
        • Lefler B.J.
        • et al.
        Melatonin entrains free-running blind people according to a physiological dose-response curve.
        Chronobiol Int. 2005; 22: 1093-1106
        • Sharkey K.M.
        • Fogg L.F.
        • Eastman C.I.
        Effects of melatonin administration on daytime sleep after simulated night shift work.
        J Sleep Res. 2001; 10: 181-192
        • Dahlitz M.J.
        • Alvarez B.
        • Vignau J.
        • et al.
        Delayed sleep phase syndrome: response to melatonin.
        Lancet. 1991; 337: 1121-1124
        • Folkard S.
        • Arendt J.
        • Clark M.
        Can melatonin improve shift workers' tolerance of the night shift? Some preliminary findings.
        Chronobiol Int. 1993; 10: 315-320
        • Arendt J.
        • Skene D.J.
        • Middleton B.
        • et al.
        Efficacy of melatonin treatment in jet lag, shift work, and blindness.
        J Biol Rhythms. 1997; 12: 604-617
        • Nagtegaal J.E.
        • Kerkhof G.A.
        • Smits M.G.
        • et al.
        Delayed sleep phase syndrome: a placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset.
        J Sleep Res. 1998; 7: 135-143
        • Dawson D.
        • Encel N.
        • Lushington K.
        Improving adaptation to simulated night shift: timed exposure to bright light versus daytime melatonin administration.
        Sleep. 1995; 18: 11-21
        • Spitzer R.L.
        • Terman M.
        • Williams J.B.
        • et al.
        Jet lag: clinical features, validation of a new syndrome-specific scale, and lack of response to melatonin in a randomized, double-blind trial.
        Am J Psychiatry. 1999; 156: 1392-1396
        • Arendt J.
        Does melatonin improve sleep? Efficacy of melatonin.
        BMJ. 2006; 332: 550
        • Nakagawa H.
        • Sack R.L.
        • Lewy A.J.
        Sleep propensity free-runs with the temperature, melatonin and cortisol rhythms in a totally blind person.
        Sleep. 1992; 15: 330-336
        • Dijk D.J.
        • Cajochen C.
        Melatonin and the circadian regulation of sleep initiation, consolidation, structure, and the sleep EEG.
        J Biol Rhythms. 1997; 12: 627-635
        • Lockley S.W.
        • Skene D.J.
        • Tabandeh H.
        • et al.
        Relationship between napping and melatonin in the blind.
        J Biol Rhythms. 1997; 12: 16-25
        • Wyatt J.K.
        • Ritz-De Cecco A.
        • Czeisler C.A.
        • et al.
        Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day.
        Am J Physiol. 1999; 277 (Regulatory, Integrative and Comparative Physiology): R1152-R1163
        • Wehr T.A.
        • Aeschbach D.
        • Duncan Jr., W.C.
        Evidence for a biological dawn and dusk in the human circadian timing system.
        J Physiol. 2001; 535: 937-951
        • Scheer F.A.
        • Zeitzer J.M.
        • Ayas N.T.
        • et al.
        Reduced sleep efficiency in cervical spinal cord injury: association with abolished night time melatonin secretion.
        Spinal Cord. 2006; 44: 78-81
        • Wright Jr., K.P.
        • Rogers N.L.
        Endogenous versus exogenous effects of melatonin.
        in: Pandi-Perumal S.R. Cardinali D.P. Melatonin: from molecules to therapy. Nova Science Publishers, New York2007: 547-569
        • Cramer H.
        • Rudolph J.
        • Consbruch U.
        • et al.
        On the effects of melatonin on sleep and behavior in man.
        Adv Biochem Psychopharmacol. 1974; 11: 187-191
        • Anton-Tay F.
        • Diaz J.L.
        • Fernandez-Guardiola A.
        On the effect of melatonin upon human brain: its possible therapeutic implications.
        Life Sci. 1971; 1015: 841-850
        • Cajochen C.
        • Krauchi K.
        • Danilenko K.V.
        • et al.
        Evening administration of melatonin and bright light: interactions on the EEG during sleep and wakefulness.
        J Sleep Res. 1998; 7: 145-157
        • Hughes R.J.
        • Badia P.
        Sleep-promoting and hypothermic effects of daytime melatonin administration in humans.
        Sleep. 1997; 20: 124-131
        • Mishima K.
        • Satoh K.
        • Shimizu T.
        • et al.
        Hypnotic and hypothermic action of daytime-administered melatonin.
        Psychopharmacol. 1997; 133: 168-171
        • Nave R.
        • Peled R.
        • Lavie P.
        Melatonin improves evening napping.
        Eur J Pharmacol. 1995; 275: 213-216
        • Zhdanova I.V.
        • Wurtman R.J.
        • Morabito C.
        • et al.
        Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans.
        Sleep. 1996; 19: 423-431
        • Reid K.
        • Van den Heuvel C.
        • Dawson D.
        Day-time melatonin administration: effects on core temperature and sleep onset latency.
        J Sleep Res. 1996; 5: 150-154
        • Gilbert S.S.
        • Van den Heuvel C.
        • Dawson D.
        Daytime melatonin and temazepam in young adult humans: equivalent effects on sleep latency and body temperatures.
        J Physiol. 1999; 514: 905-914
        • Wyatt J.K.
        • Dijk D.J.
        • Ritz-de Cecco A.
        • et al.
        Sleep-facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase dependent.
        Sleep. 2006; 29: 609-618
        • Waldhauser F.
        • Saletu B.
        • Trinchard-Lugan I.
        Sleep laboratory investigations on hypnotic properties of melatonin.
        Psychopharmacology (Berl). 1990; 100: 222-226
        • Attenburrow M.E.
        • Cowen P.J.
        • Sharpley A.L.
        Low dose melatonin improves sleep in healthy middle-aged subjects.
        Psychopharmacology (Berl). 1996; 126: 179-181
        • Cajochen C.
        • Krauchi K.
        • Mori D.
        • et al.
        Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis.
        Am J Phys. 1997; 272: R1189-R1196
        • Dawson D.
        • Rogers N.L.
        • van den Heuvel C.J.
        • et al.
        Effect of sustained nocturnal transbuccal melatonin administration on sleep and temperature in elderly insomniacs.
        J Biol Rhythms. 1998; 13: 532-538
        • Middleton B.A.
        • Stone B.M.
        • Arendt J.
        Melatonin and fragmented sleep patterns.
        Lancet. 1996; 348: 551-552
        • Nave R.
        • Herer P.
        • Haimov I.
        • et al.
        Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of antagonism by flumazenil.
        Neurosci Lett. 1996; 214: 123-126
        • Tzischinsky O.
        • Lavie P.
        Melatonin possesses time-dependent hypnotic effects.
        Sleep. 1994; 17: 638-645
        • Zhdanova I.V.
        • Wurtman R.J.
        Efficacy of melatonin as a sleep-promoting agent.
        J Biol Rhythms. 1997; 12: 644-650
        • Dijk D.J.
        • Roth C.
        • Landolt H.P.
        • et al.
        Melatonin effect on daytime sleep in men: suppression of EEG low frequency activity and enhancement of spindle frequency activity.
        Neurosci Lett. 1995; 201: 13-16
        • Stone B.M.
        • Turner C.
        • Mills S.L.
        • et al.
        Hypnotic activity of melatonin.
        Sleep. 2000; 23: 663-669
        • Lavie P.
        Ultrashort sleep-waking schedule. III. ‘Gates’ and ‘forbidden zones’ for sleep.
        Electroencephalogr Clin Neurophysiol. 1986; 63: 414-425
        • Strogatz S.H.
        • Kronauer R.E.
        • Czeisler C.A.
        Circadian regulation dominates homeostatic control of sleep length and prior wake length in humans.
        Sleep. 1986; 9: 353-364
        • Garfinkel D.
        • Laudon M.
        • Nof D.
        • et al.
        Improvement of sleep quality in elderly people by controlled-release melatonin.
        Lancet. 1995; 346: 541-544
        • Haimov I.
        • Lavie P.
        • Laudon M.
        • et al.
        Melatonin replacement therapy of elderly insomniacs.
        Sleep. 1995; 18: 598-603
        • MacFarlane J.G.
        • Cleghorn J.M.
        • Brown G.M.
        • et al.
        The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study.
        Biol Psychiatry. 1991; 30: 371-376
        • Wurtman R.J.
        • Zhdanova I.
        Improvement of sleep quality by melatonin.
        Lancet. 1995; 346: 1491
        • Zhdanova I.V.
        • Wurtman R.J.
        • Regan M.M.
        • et al.
        Melatonin treatment for age-related insomnia.
        J Clin Endocrinol Metab. 2001; 86: 4727-4730
        • Ellis C.M.
        • Lemmens G.
        • Parkes J.D.
        Melatonin and insomnia.
        J Sleep Res. 1996; 5: 61-65
        • James S.P.
        • Sack D.A.
        • Rosenthal N.E.
        • et al.
        Melatonin administration in insomnia.
        Neuropsychopharmacology. 1990; 3: 19-23
        • Dagan Y.
        Circadian rhythm sleep disorders (CRSD) in psychiatry: a review.
        Isr J Psychiatry Relat Sci. 2002; 39: 19-27
        • Chou T.C.
        • Bjorkum A.A.
        • Gaus S.E.
        • et al.
        Afferents to the ventrolateral preoptic nucleus.
        J Neurosci. 2002; 22: 977-990
        • Deurveilher S.
        • Semba K.
        Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state.
        Neurosci. 2005; 130: 165-183
        • Aston-Jones G.
        • Chen S.
        • Zhu Y.
        • et al.
        A neural circuit for circadian regulation of arousal.
        Nat Neurosci. 2001; 4: 732-738
        • Deboer T.
        • Overeem S.
        • Visser N.A.
        • et al.
        Convergence of circadian and sleep regulatory mechanisms on hypocretin-1.
        Neuroscience. 2004; 129: 727-732
        • Zeitzer J.M.
        • Buckmaster C.L.
        • Parker K.J.
        • et al.
        Circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness.
        J Neurosci. 2003; 23: 3555-3560
        • Zhang S.
        • Zeitzer J.M.
        • Yoshida Y.
        • et al.
        Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release.
        Sleep. 2004; 27: 619-627
        • Cajochen C.
        • Krauchi K.
        • Wirz-Justice A.
        Role of melatonin in the regulation of human circadian rhythms and sleep.
        J Neuroendocrinol. 2003; 15: 432-437
        • Cagnacci A.
        • Elliott J.A.
        • Yen S.S.
        Melatonin: a major regulator of the circadian rhythm of core temperature in humans.
        J Clin Endocrinol Metab. 1992; 75: 447-452
        • Krauchi K.
        • Cajochen C.
        • Werth E.
        • et al.
        Warm feet promote the rapid onset of sleep.
        Nature. 1999; 401: 36-37
        • Burgess H.J.
        • Sletten T.
        • Savic N.
        • et al.
        Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night.
        J Appl Phys. 2001; 91: 1214-1222
        • Cagnacci A.
        • Soldani R.
        • Yen S.S.C.
        The effect of light on core body temperature is mediated by melatonin in women.
        J Clin Endocrinol Metab. 1993; 76: 1036-1038
        • Wright K.P.
        • Badia P.
        • Myers B.L.
        • et al.
        Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans.
        Brain Res. 1997; 747: 78-84
        • Wright Jr., K.P.
        • Myers B.L.
        • Plenzler S.C.
        • et al.
        Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives.
        Brain Res. 2000; 873: 310-317
        • Cagnacci A.
        • Soldani R.
        • Romagnolo C.
        • et al.
        Melatonin-induced decrease of body temperature in women: a threshold event.
        Neuroendocrinology. 1994; 60: 549-552
        • van den Heuvel C.J.
        • Reid K.J.
        • Dawson D.
        Effect of atenolol on nocturnal sleep and temperature in young men: reversal by pharmacological doses of melatonin.
        Physiol Behav. 1997; 61: 795-802
        • Dollins A.B.
        • Lynch H.J.
        • Wurtman R.J.
        • et al.
        Effect of pharmacological daytime doses of melatonin on human mood and performance.
        Psychopharmacology. 1993; 112: 490-496
        • Dawson D.
        • Gibbon S.
        • Singh P.
        The hypothermic effect of melatonin on core body temperature: is more better?.
        J Pineal Res. 1996; 20: 192-197
        • Satoh K.
        • Mishima K.
        Hypothermic action of exogenously administered melatonin is dose dependent in humans.
        Clin Neuropharmacol. 2001; 24: 334-340
        • van den Heuvel C.J.
        • Kennaway D.J.
        • Dawson D.
        Thermoregulatory and soporific effects of very low dose melatonin injection.
        Am J Physiol. 1999; 276: E249-E254
        • Rogers N.L.
        • Phan O.
        • Kennaway D.J.
        • et al.
        Effect of daytime oral melatonin administration on neurobehavioral performance in humans.
        J Pineal Res. 1998; 25: 47-53
        • Rogers N.L.
        • Kennaway D.J.
        • Dawson D.
        Neurobehavioural performance effects of daytime melatonin and temazepam administration.
        J Sleep Res. 2003; 12: 207-212
        • Suhner A.
        • Schlagenhauf P.
        • Tschopp A.
        • et al.
        Impact of melatonin on driving performance.
        J Travel Med. 1998; 5: 7-13
        • Wynn V.T.
        • Arendt J.
        Effect of melatonin on the human electrocardiogram and simple reaction time responses.
        J Pineal Res. 1988; 5: 427-435
        • Graw P.
        • Werth E.
        • Krauchi K.
        • et al.
        Early morning melatonin administration impairs psychomotor vigilance.
        Behav Brain Res. 2001; 121: 167-172
        • Cajochen C.
        • Kraeuchi K.
        • Wirz-Justice A.
        The acute soporific action of daytime melatonin administration: effects on the EEG during wakefulness and subjective alertness.
        J Biol Rhythms. 1997; 12: 636-643
        • Zhdanova I.V.
        • Wurtman R.J.
        • Lynch H.J.
        • et al.
        Sleep-inducing effects of low doses of melatonin ingested in the evening.
        Clin Pharmacol Ther. 1995; 57: 552-558
        • Nave R.
        • Iani C.
        • Herer P.
        • et al.
        Residual effects of daytime administration of melatonin on performance relevant to flight.
        Behav Brain Res. 2002; 131: 87-95
        • Kato K.
        • Hirai K.
        • Nishiyama K.
        • et al.
        Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist.
        Neuropharmacology. 2005; 48: 301-310
        • Rozerem
        • (ramelteon tablets)
        Package insert.
        Takeda Pharmaceuticals, 2005
        • Stevenson S.
        • Cornelissen K.
        • Clarke E.
        • et al.
        Study of the absorption, metabolism, and excretion of (14C)-ramelteon (TAK-375).
        Clin Pharmacol Ther. 2004; 75 ([abstract]): 22
        • Karim A.
        • Tolbert D.
        • Cao C.
        Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia.
        J Clin Pharmacol. 2006; 46: 140-148
        • Hirai K.
        • Kita M.
        • Ohta H.
        • et al.
        Ramelteon (TAK-375) accelerates reentrainment of circadian rhythm after a phase advance of the light-dark cycle in rats.
        J Biol Rhythms. 2005; 20: 27-37
        • Miyamoto M.
        • Nishikawa H.
        • Doken Y.
        • et al.
        The sleep-promoting action of ramelteon (TAK-375) in freely moving cats.
        Sleep. 2004; 27: 1319-1325
        • Miyamoto M.
        Effect of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist, on motor performance in mice.
        Neurosci Lett. 2006; 402: 201-204
        • France C.P.
        • Weltman R.H.
        • Koek W.
        • et al.
        Acute and chronic effects of ramelteon in rhesus monkeys (Macaca mulatta): dependence liability studies.
        Behav Neurosci. 2006; 120: 535-541
        • Miyamoto M.
        • Nishikawa H.
        • Ohta H.
        • et al.
        Behavioral pharmacology of ramelteon (TAK-375) in small animals.
        Ann Neurol. 2003; 54 ([abstract]): S46
        • Yukuhiro N.
        • Kimura H.
        • Nishikawa H.
        • et al.
        Effects of ramelteon (TAK-375) on nocturnal sleep in freely moving monkeys.
        Brain Res. 2004; 1027: 59-66
        • Fisher S.P.
        • Davidson K.
        • Kulla A.
        • et al.
        Acute sleep-promoting action of the melatonin agonist, ramelteon, in the rat.
        J Pineal Res. 2008; 45: 125-135
        • Rawashdeh O.
        • Stepien I.
        • Smith M.
        • et al.
        Phase response curve for ramelteon in C3H/HeN mice.
        Society for Biological Rhythms Program and Abstracts. 2008; 190
        • Zee P.
        • Richardson G.
        • Wang-Weigand S.
        Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel.
        Society for Biological Rhythms Program and Abstracts. 2008; 70
        • Richardson G.S.
        • Zee P.C.
        • Wang-Weigand S.
        • et al.
        Circadian phase-shifting effects of repeated ramelteon administration in healthy adults.
        J Clin Sleep Med. 2008; 4: 456-461
        • Roth T.
        • Stubbs C.
        • Walsh J.K.
        Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment.
        Sleep. 2005; 28: 303-307
        • Zammit G.
        • Schwartz H.
        • Roth T.
        • et al.
        The effects of ramelteon in a first-night model of transient insomnia.
        Sleep Med. 2009; 10: 55-59
        • Erman M.
        • Seiden D.
        • Zammit G.
        • et al.
        An efficacy, safety, and dose-response study of ramelteon in patients with chronic primary insomnia.
        Sleep Med. 2006; 7: 17-24
        • Roth T.
        • Seiden D.
        • Wang-Weigand S.
        • et al.
        A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia.
        Curr Med Res Opin. 2007; 23: 1005-1014
        • Zammit G.
        • Erman M.
        • Wang-Weigand S.
        • et al.
        Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia.
        J Clin Sleep Med. 2007; 3: 495-504
        • Roth T.
        • Seiden D.
        • Sainati S.
        • et al.
        Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia.
        Sleep Med. 2006; 7: 312-318
        • Johnson M.W.
        • Suess P.E.
        • Griffiths R.R.
        Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects.
        Arch Gen Psychiatry. 2006; 63: 1149-1157
        • Kryger M.
        • Wang-Weigand S.
        • Roth T.
        Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea.
        Sleep Breath. 2007; 11: 159-164
        • Kryger M.
        • Roth T.
        • Wang-Weigand S.
        • et al.
        The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease.
        Sleep Breath. 2009; 13: 79-84
        • Kryger M.
        • Wang-Weigand S.
        • Zhang J.
        • et al.
        Effect of ramelteon, a selective MT(1)/MT(2)-receptor agonist, on respiration during sleep in mild to moderate COPD.
        Sleep Breath. 2008; 12: 243-250
        • Millan M.J.
        • Gobert A.
        • Lejeune F.
        • et al.
        The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine-2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways.
        J Pharmacol Exp Ther. 2003; 306: 954-964
        • Turek F.W.
        • Gillette M.U.
        Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists.
        Sleep Med. 2004; 5: 523-532
        • Leproult R.
        • Van Onderbergen A.
        • L'Hermite-Baleriaux M.
        • et al.
        Phase shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men.
        Clin Endocrinol (Oxf). 2005; 63: 298-304
        • Boivin D.B.
        Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders.
        J Psychiatry Neurosci. 2000; 25: 446-458
        • Tsujimoto T.
        • Yamada N.
        • Shimoda K.
        • et al.
        Circadian rhythms in depression. Part II. Circadian rhythms in inpatients with various mental disorders.
        J Affect Disord. 1990; 18: 199-210
        • Dalton E.J.
        • Rotondi D.
        • Levitan R.D.
        • et al.
        Use of slow-release melatonin in treatment-resistant depression.
        J Psychiatry Neurosci. 2000; 25: 48-52
        • Zupancic M.
        • Guilleminault C.
        Agomelatine: a preliminary review of a new antidepressant.
        CNS Drugs. 2006; 20: 981-992
        • Pandi-Perumal S.R.
        • Srinivasan V.
        • Maestroni G.J.
        • et al.
        Melatonin: nature's most versatile biological signal?.
        FEBS J. 2006; 273: 2813-2838
        • Loo H.
        • Hale A.
        • D'Haenen H.
        Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study.
        Int Clin Psychopharmacol. 2002; 17: 239-247
        • Kennedy S.H.
        • Emsley R.
        Placebo-controlled trial of agomelatine in the treatment of major depressive disorder.
        Eur Neuropsychopharmacol. 2006; 16: 93-100
        • Olie J.P.
        • Emsley R.
        Confirmed clinical efficacy of agomelatine (25–50 mg) in major depression: two randomized, double-blind, placebo-controlled studies.
        Eur Neuropsychopharmacol. 2005; 15: S416
        • Olie J.P.
        • Kasper S.
        Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder.
        Int J Neuropsychopharmacol. 2007; 10: 661-673
        • Rajaratnam S.M.
        • Rajaratnam M.H.
        • Fisher D.M.
        • et al.
        Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled trials.
        Lancet. 2009; 373: 482-491
        • Vachharajani N.N.
        • Yeleswaram K.
        • Boulton D.W.
        Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist.
        J Pharm Sci. 2003; 92: 760-772
        • Nickelsen T.
        • Samel A.
        • Vejvoda M.
        • et al.
        Chronobiotic effects of the melatonin agonist LY 156735 following a simulated 9 h time shift: results of a placebo-controlled trial.
        Chronobiol Int. 2002; 19: 915-936
        • Mulchahey J.J.
        • Goldwater D.R.
        • Zemlan F.P.
        A single blind, placebo controlled, across group dose escalation study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the melatonin analog beta-methyl-6-chloromelatonin.
        Life Sci. 2004; 75: 1843-1856
        • Zemlan F.P.
        • Mulchahey J.J.
        • Scharf M.B.
        • et al.
        The efficacy and safety of the melatonin agonist beta-methyl-6-chloromelatonin in primary insomnia: a randomized, placebo-controlled, crossover clinical trial.
        J Clin Psychiatry. 2005; 66: 384-390
        • Maquet P.
        The role of sleep in learning and memory.
        Science. 2001; 294: 1048-1052
        • Walker M.P.
        • Stickgold R.
        Sleep, memory, and plasticity.
        Annu Rev Psychol. 2006; 57: 139-166
        • Graves L.
        • Pack A.
        • Abel T.
        Sleep and memory: a molecular perspective.
        Trends Neurosci. 2001; 24: 237-243
        • Stickgold R.
        • Walker M.P.
        Sleep and memory: the ongoing debate.
        Sleep. 2005; 28: 1225-1227
        • Lyons L.C.
        • Rawashdeh O.
        • Katzoff A.
        • et al.
        Circadian modulation of complex learning in diurnal and nocturnal Aplysia.
        Proc Natl Acad Sci U S A. 2005; 102: 12589-12594
        • Dana R.C.
        • Martinez Jr., J.L.
        Effect of adrenalectomy on the circadian rhythm of LTP.
        Brain Res. 1984; 308: 392-395
        • Chaudhury D.
        • Wang L.M.
        • Colwell C.S.
        Circadian regulation of hippocampal long-term potentiation.
        J Biol Rhythms. 2005; 20: 225-236
        • Claridge-Chang A.
        • Wijnen H.
        • Naef F.
        • et al.
        Circadian regulation of gene expression systems in the Drosophila head.
        Neuron. 2001; 32: 657-671
        • Imbesi M.
        • Uz T.
        • Dzitoyeva S.
        • et al.
        Stimulatory effects of a melatonin receptor agonist, ramelteon, on BDNF in mouse cerebellar granule cells.
        Neurosci Lett. 2008; 439: 34-36
        • Imbesi M.
        • Uz T.
        • Manev H.
        Melatonin receptor agonist ramelteon activates the extracellular signal-regulated kinase 1/2 in mouse cerebellar granule cells.
        Neuroscience. 2008; 155: 1160-1164