Melatonin and Melatonin Analogues

Sleep Medicine Clinics

Volumn 4, Issue 2, 2009, Pages 179-193

  Rajaratnam, Shantha M W ^a,b,c   Cohen, Daniel A ^b,c,d   Rogers, Naomi L ^e  

^a MONASH UNIVERSITY   (Australia)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^e UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Agomelatine; Circadian rhythm; Melatonin; Melatonin agonist; PD 6735; Ramelteon; Sleep; Tasimelteon

Indexed keywords

4P PDOT; AGOMELATINE; ATENOLOL; BENZODIAZEPINE DERIVATIVE; BMS 214778; FLUVOXAMINE; HYPNOTIC AGENT; MELATONIN; MELATONIN DERIVATIVE; MELATONIN RECEPTOR; N [2 (6 CHLORO 5 METHOXY 1H INDOL 3 YL)PROPYL]ACETAMIDE; PD 6735; PLACEBO; RAMELTEON; TASIMELTEON; TRIAZOLAM; UNCLASSIFIED DRUG; VEC 162; ZOLPIDEM;

AREA UNDER THE CURVE; BEDTIME DOSAGE; BRADYCARDIA; CIRCADIAN RHYTHM; CIRCADIAN RHYTHM SLEEP DISORDER; CLINICAL TRIAL; COGNITION; COGNITIVE DEFECT; DIZZINESS; DROWSINESS; DRUG ABSORPTION; DRUG ABUSE; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG METABOLISM; EVENING DOSAGE; HORMONAL REGULATION; HORMONE ACTION; HUMAN; HYPOTENSION; HYPOTHERMIA; INSOMNIA; JET LAG; LOW DRUG DOSE; MORNING DOSAGE; NAUSEA; NONHUMAN; OXYGEN SATURATION; PRIORITY JOURNAL; REBOUND; RECOMMENDED DRUG DOSE; REPEATED DRUG DOSE; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SLEEP APNEA SYNDROME; SLEEP DISORDER; SLEEP TIME; WITHDRAWAL SYNDROME;

EID: 66449112190     PISSN: 1556407X     EISSN: 15564088     Source Type: Journal    
DOI: 10.1016/j.jsmc.2009.02.007     Document Type: Review

References (175)

1. Arendt J., and Rajaratnam S.M. Melatonin and its agonists: an update. Br J Psychiatry 193 4 (2008) 267-269
2. Redman J., Armstrong S., and Ng K.T. Free-running activity rhythms in the rat: entrainment by melatonin. Science 219 (1983) 1089-1091
3. Arendt J., Bojkowski C., Folkard S., et al. Some effects of melatonin and the control of its secretion in humans. Ciba Found Symp 117 (1985) 266-283
4. Perreau-Lenz S., Kalsbeek A., Garidou M.L., et al. Suprachiasmatic control of melatonin synthesis in rats: inhibitory and stimulatory mechanisms. Eur J Neurosci 17 (2003) 221-228
5. Perreau-Lenz S., Kalsbeek A., Pevet P., et al. Glutamatergic clock output stimulates melatonin synthesis at night. Eur J Neurosci 19 (2004) 318-324
6. 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 1 (1981) 1414-1425
7. Klein D.C., and Moore R.Y. Pineal N-acetyltransferase and hydroxyindole-O-methyltransferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus. Brain Res 174 (1979) 245-262
8. Pandi-Perumal S.R., Trakht I., Srinivasan V., et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85 3 (2008) 335-353
9. Cassone V.M., Chesworth M.J., and Armstrong S.M. Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei. Physiol Behav 36 (1986) 1111-1121
10. Sumova A., and Illnerova H. Melatonin instantaneously resets intrinsic circadian rhythmicity in the rat suprachiasmatic nucleus. Neurosci Lett 218 3 (1996) 181-184
11. Cassone V.M., Roberts M.H., and Moore R.Y. Effects of melatonin on 2-deoxy-[1-14C] glucose uptake within rat suprachiasmatic nucleus. Am J Phys 255 (1988) R332-R337
12. 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 18 24 (1998) 10389-10397
13. Kopp M., Meissl H., and 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 227 3 (1997) 145-148
14. Reppert S.M., Weaver D.R., and Godson C. Melatonin receptors step into the light: cloning and classification of subtypes. Trends Pharmacol Sci 17 3 (1996) 100-102
15. Liu C., Weaver D.R., Jin X., et al. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19 1 (1997) 91-102
16. 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 280 1 (2001) C110-C118
17. 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 12 12 (1998) 1211-1220
18. 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 39 2 (2005) 113-120
19. 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 11 9 (2000) 1803-1807
20. Dubocovich M.L. Melatonin receptors: role on sleep and circadian rhythm regulation. Sleep Med 8 Suppl 3 (2007) 34-42
21. Shibata S., Cassone V.M., and Moore R.Y. Effects of melatonin on neuronal activity in the rat suprachiasmatic nucleus in vitro. Neurosci Lett 97 1-2 (1989) 140-144
22. Jin X., von Gall C., Pieschl R.L., et al. Targeted disruption of the mouse Mel(1b) melatonin receptor. Mol Cell Biol 23 3 (2003) 1054-1060
23. Lieberman H.R., Waldhauser F., Garfield G., et al. Effects of melatonin on human mood and performance. Brain Res 323 2 (1984) 201-207
24. Rogers N.L., Dinges D.F., Kennaway D.J., et al. Potential action of melatonin in insomnia. Sleep 26 8 (2003) 1058-1059
25. Hughes R.J., Sack R.L., and 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 21 1 (1998) 52-68
26. Deacon S., and Arendt J. Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res 688 1-2 (1995) 77-85
27. 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 91 (1994) 1824-1828
28. 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 332 7538 (2006) 385-393
29. Herxheimer A., and Petrie K.J. Melatonin for the prevention and treatment of jet lag (Cochrane Review). Cochrane Database Syst Rev 2 (2002) CD001520
30. 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 20 12 (2005) 1151-1158
31. Aldhous M., Franey C., Wright J., et al. Plasma concentrations of melatonin in man following oral absorption of different preparations. Br J Clin Pharmacol 19 4 (1985) 517-521
32. Waldhauser F., Waldhauser M., Lieberman H.R., et al. Bioavailability of oral melatonin in humans. Neuroendocrinology 39 4 (1984) 307-313
33. Redman J.R. Circadian entrainment and phase shifting in mammals with melatonin. J Biol Rhythms 12 6 (1997) 581-587
34. McArthur A.J., Hunt A.E., and Gillette M.U. Melatonin and signal transduction in the rat suprachiasmatic circadian clock: activation of protein kinase C at dawn and dusk. Endocrinology 138 (1997) 627-634
35. Arendt J., Middleton B., Stone B., et al. Complex effects of melatonin: evidence for photoperiodic responses in humans?. Sleep 22 5 (1999) 625-635
36. Burgess H.J., Revell V.L., and Eastman C.I. A three pulse phase response curve to three milligrams of melatonin in humans. J Physiol 586 2 (2008) 639-647
37. 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 15 1 (1998) 71-83
38. Zaidan R., Geoffriau M., Brun J., et al. Melatonin is able to influence its secretion in humans: description of a phase response curve. Neuroendocrinology 60 (1994) 105-112
39. 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 32 1 (2002) 1-5
40. Sack R.L., Lewy A.J., and Hoban T.M. Free-running melatonin rhythms in blind people: phase shifts with melatonin and triazolam administration. In: Rensing L., van der Heiden U., and Mackey M.C. (Eds). Temporal disorder in human oscillatory systems (1987), Springer-Verlag, Heidelberg 219-224
41. Deacon S., English J., and Arendt J. Acute phase-shifting effects of melatonin associated with suppression of core body temperature in humans. Neurosci Lett 178 1 (1994) 32-34
42. Attenburrow M.E.J., Dowling B.A., Sargent P.A., et al. Melatonin phase advances circadian rhythm. Psychopharmacology (Berl) 121 4 (1995) 503-505
43. 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 272 4 Pt 2 (1997) R1178-R1188
44. Sharkey K.M., and Eastman C.I. Melatonin phase shifts human circadian rhythms in a placebo-controlled simulated night-work study. Am J Physiol Regul Integr Comp Physiol 282 2 (2002) R454-R463
45. 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 88 9 (2003) 4303-4309
46. 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 16 2 (2007) 148-155
47. 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 561 Pt 1 (2004) 339-351
48. Lockley S.W., Skene D.J., James K., et al. Melatonin administration can entrain the free-running circadian system of blind subjects. J Endocrinol 164 (2000) R1-R6
49. 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 343 15 (2000) 1070-1077
50. 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 19 3 (2002) 649-658
51. 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 18 5 (2003) 420-429
52. 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 22 6 (2005) 1093-1106
53. Sharkey K.M., Fogg L.F., and Eastman C.I. Effects of melatonin administration on daytime sleep after simulated night shift work. J Sleep Res 10 3 (2001) 181-192
54. Dahlitz M.J., Alvarez B., Vignau J., et al. Delayed sleep phase syndrome: response to melatonin. Lancet 337 (1991) 1121-1124
55. Folkard S., Arendt J., and Clark M. Can melatonin improve shift workers' tolerance of the night shift? Some preliminary findings. Chronobiol Int 10 5 (1993) 315-320
56. Arendt J., Skene D.J., Middleton B., et al. Efficacy of melatonin treatment in jet lag, shift work, and blindness. J Biol Rhythms 12 6 (1997) 604-617
57. 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 7 2 (1998) 135-143
58. Dawson D., Encel N., and Lushington K. Improving adaptation to simulated night shift: timed exposure to bright light versus daytime melatonin administration. Sleep 18 1 (1995) 11-21
59. 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 156 9 (1999) 1392-1396
60. Arendt J. Does melatonin improve sleep? Efficacy of melatonin. BMJ 332 7540 (2006) 550
61. Nakagawa H., Sack R.L., and Lewy A.J. Sleep propensity free-runs with the temperature, melatonin and cortisol rhythms in a totally blind person. Sleep 15 4 (1992) 330-336
62. Dijk D.J., and Cajochen C. Melatonin and the circadian regulation of sleep initiation, consolidation, structure, and the sleep EEG. J Biol Rhythms 12 6 (1997) 627-635
63. Lockley S.W., Skene D.J., Tabandeh H., et al. Relationship between napping and melatonin in the blind. J Biol Rhythms 12 1 (1997) 16-25
64. 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. (Regulatory, Integrative and Comparative Physiology). Am J Physiol 277 46 (1999) R1152-R1163
65. Wehr T.A., Aeschbach D., and Duncan Jr. W.C. Evidence for a biological dawn and dusk in the human circadian timing system. J Physiol 535 Pt 3 (2001) 937-951
66. 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 44 2 (2006) 78-81
67. Wright Jr. K.P., and Rogers N.L. Endogenous versus exogenous effects of melatonin. In: Pandi-Perumal S.R., and Cardinali D.P. (Eds). Melatonin: from molecules to therapy (2007), Nova Science Publishers, New York 547-569
68. Cramer H., Rudolph J., Consbruch U., et al. On the effects of melatonin on sleep and behavior in man. Adv Biochem Psychopharmacol 11 (1974) 187-191
69. Anton-Tay F., Diaz J.L., and Fernandez-Guardiola A. On the effect of melatonin upon human brain: its possible therapeutic implications. Life Sci 1015 (1971) 841-850
70. 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 7 3 (1998) 145-157
71. Hughes R.J., and Badia P. Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep 20 2 (1997) 124-131
72. Mishima K., Satoh K., Shimizu T., et al. Hypnotic and hypothermic action of daytime-administered melatonin. Psychopharmacol 133 (1997) 168-171
73. Nave R., Peled R., and Lavie P. Melatonin improves evening napping. Eur J Pharmacol 275 2 (1995) 213-216
74. 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 19 5 (1996) 423-431
75. Reid K., Van den Heuvel C., and Dawson D. Day-time melatonin administration: effects on core temperature and sleep onset latency. J Sleep Res 5 3 (1996) 150-154
76. Gilbert S.S., Van den Heuvel C., and Dawson D. Daytime melatonin and temazepam in young adult humans: equivalent effects on sleep latency and body temperatures. J Physiol 514 Pt 3 (1999) 905-914
77. 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 29 5 (2006) 609-618
78. Waldhauser F., Saletu B., and Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl) 100 2 (1990) 222-226
79. Attenburrow M.E., Cowen P.J., and Sharpley A.L. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl) 126 2 (1996) 179-181
80. 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 272 4 Pt 2 (1997) R1189-R1196
81. 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 13 (1998) 532-538
82. Middleton B.A., Stone B.M., and Arendt J. Melatonin and fragmented sleep patterns. Lancet 348 9026 (1996) 551-552
83. 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 214 2-3 (1996) 123-126
84. Tzischinsky O., and Lavie P. Melatonin possesses time-dependent hypnotic effects. Sleep 17 7 (1994) 638-645
85. Zhdanova I.V., and Wurtman R.J. Efficacy of melatonin as a sleep-promoting agent. J Biol Rhythms 12 6 (1997) 644-650
86. 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 201 1 (1995) 13-16
87. Stone B.M., Turner C., Mills S.L., et al. Hypnotic activity of melatonin. Sleep 23 5 (2000) 663-669
88. Lavie P. Ultrashort sleep-waking schedule. III. 'Gates' and 'forbidden zones' for sleep. Electroencephalogr Clin Neurophysiol 63 5 (1986) 414-425
89. Strogatz S.H., Kronauer R.E., and Czeisler C.A. Circadian regulation dominates homeostatic control of sleep length and prior wake length in humans. Sleep 9 2 (1986) 353-364
90. Garfinkel D., Laudon M., Nof D., et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 346 8974 (1995) 541-544
91. Haimov I., Lavie P., Laudon M., et al. Melatonin replacement therapy of elderly insomniacs. Sleep 18 7 (1995) 598-603
92. 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 30 (1991) 371-376
93. Wurtman R.J., and Zhdanova I. Improvement of sleep quality by melatonin. Lancet 346 8988 (1995) 1491
94. Zhdanova I.V., Wurtman R.J., Regan M.M., et al. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 86 10 (2001) 4727-4730
95. Ellis C.M., Lemmens G., and Parkes J.D. Melatonin and insomnia. J Sleep Res 5 1 (1996) 61-65
96. James S.P., Sack D.A., Rosenthal N.E., et al. Melatonin administration in insomnia. Neuropsychopharmacology 3 (1990) 19-23
97. Dagan Y. Circadian rhythm sleep disorders (CRSD) in psychiatry: a review. Isr J Psychiatry Relat Sci 39 1 (2002) 19-27
98. Chou T.C., Bjorkum A.A., Gaus S.E., et al. Afferents to the ventrolateral preoptic nucleus. J Neurosci 22 (2002) 977-990
99. Deurveilher S., and 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 130 (2005) 165-183
100. Aston-Jones G., Chen S., Zhu Y., et al. A neural circuit for circadian regulation of arousal. Nat Neurosci 4 (2001) 732-738
101. Deboer T., Overeem S., Visser N.A., et al. Convergence of circadian and sleep regulatory mechanisms on hypocretin-1. Neuroscience 129 (2004) 727-732
102. 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 23 (2003) 3555-3560
103. Zhang S., Zeitzer J.M., Yoshida Y., et al. Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release. Sleep 27 (2004) 619-627
104. Cajochen C., Krauchi K., and Wirz-Justice A. Role of melatonin in the regulation of human circadian rhythms and sleep. J Neuroendocrinol 15 4 (2003) 432-437
105. Cagnacci A., Elliott J.A., and Yen S.S. Melatonin: a major regulator of the circadian rhythm of core temperature in humans. J Clin Endocrinol Metab 75 (1992) 447-452
106. Krauchi K., Cajochen C., Werth E., et al. Warm feet promote the rapid onset of sleep. Nature 401 6748 (1999) 36-37
107. 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 91 (2001) 1214-1222
108. Cagnacci A., Soldani R., and Yen S.S.C. The effect of light on core body temperature is mediated by melatonin in women. J Clin Endocrinol Metab 76 4 (1993) 1036-1038
109. 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 747 (1997) 78-84
110. 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 873 (2000) 310-317
111. Cagnacci A., Soldani R., Romagnolo C., et al. Melatonin-induced decrease of body temperature in women: a threshold event. Neuroendocrinology 60 5 (1994) 549-552
112. van den Heuvel C.J., Reid K.J., and Dawson D. Effect of atenolol on nocturnal sleep and temperature in young men: reversal by pharmacological doses of melatonin. Physiol Behav 61 (1997) 795-802
113. Dollins A.B., Lynch H.J., Wurtman R.J., et al. Effect of pharmacological daytime doses of melatonin on human mood and performance. Psychopharmacology 112 4 (1993) 490-496
114. Dawson D., Gibbon S., and Singh P. The hypothermic effect of melatonin on core body temperature: is more better?. J Pineal Res 20 4 (1996) 192-197
115. Satoh K., and Mishima K. Hypothermic action of exogenously administered melatonin is dose dependent in humans. Clin Neuropharmacol 24 (2001) 334-340
116. van den Heuvel C.J., Kennaway D.J., and Dawson D. Thermoregulatory and soporific effects of very low dose melatonin injection. Am J Physiol 276 (1999) E249-E254
117. Rogers N.L., Phan O., Kennaway D.J., et al. Effect of daytime oral melatonin administration on neurobehavioral performance in humans. J Pineal Res 25 (1998) 47-53
118. Rogers N.L., Kennaway D.J., and Dawson D. Neurobehavioural performance effects of daytime melatonin and temazepam administration. J Sleep Res 12 (2003) 207-212
119. Suhner A., Schlagenhauf P., Tschopp A., et al. Impact of melatonin on driving performance. J Travel Med 5 1 (1998) 7-13
120. Wynn V.T., and Arendt J. Effect of melatonin on the human electrocardiogram and simple reaction time responses. J Pineal Res 5 (1988) 427-435
121. Graw P., Werth E., Krauchi K., et al. Early morning melatonin administration impairs psychomotor vigilance. Behav Brain Res 121 (2001) 167-172
122. Cajochen C., Kraeuchi K., and Wirz-Justice A. The acute soporific action of daytime melatonin administration: effects on the EEG during wakefulness and subjective alertness. J Biol Rhythms 12 6 (1997) 636-643
123. 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 57 5 (1995) 552-558
124. Nave R., Iani C., Herer P., et al. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res 131 (2002) 87-95
125. Kato K., Hirai K., Nishiyama K., et al. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology 48 2 (2005) 301-310
126. Rozerem, and (ramelteon tablets). Package insert (2005), Takeda Pharmaceuticals
127. Stevenson S., Cornelissen K., Clarke E., et al. Study of the absorption, metabolism, and excretion of (14C)-ramelteon (TAK-375). [abstract]. Clin Pharmacol Ther 75 (2004) 22
128. Karim A., Tolbert D., and 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 46 2 (2006) 140-148
129. 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 20 1 (2005) 27-37
130. Miyamoto M., Nishikawa H., Doken Y., et al. The sleep-promoting action of ramelteon (TAK-375) in freely moving cats. Sleep 27 7 (2004) 1319-1325
131. Miyamoto M. Effect of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist, on motor performance in mice. Neurosci Lett 402 3 (2006) 201-204
132. 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 120 3 (2006) 535-541
133. Miyamoto M., Nishikawa H., Ohta H., et al. Behavioral pharmacology of ramelteon (TAK-375) in small animals. [abstract]. Ann Neurol 54 Suppl 7 (2003) S46
134. Yukuhiro N., Kimura H., Nishikawa H., et al. Effects of ramelteon (TAK-375) on nocturnal sleep in freely moving monkeys. Brain Res 1027 1-2 (2004) 59-66
135. Fisher S.P., Davidson K., Kulla A., et al. Acute sleep-promoting action of the melatonin agonist, ramelteon, in the rat. J Pineal Res 45 2 (2008) 125-135
136. Rawashdeh O., Stepien I., Smith M., et al. Phase response curve for ramelteon in C3H/HeN mice. Society for Biological Rhythms Program and Abstracts 190 (2008)
137. Zee P., Richardson G., and Wang-Weigand S. Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel. Society for Biological Rhythms Program and Abstracts 70 (2008)
138. 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 4 5 (2008) 456-461
139. Roth T., Stubbs C., and 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 28 3 (2005) 303-307
140. Zammit G., Schwartz H., Roth T., et al. The effects of ramelteon in a first-night model of transient insomnia. Sleep Med 10 1 (2009) 55-59
141. 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 7 1 (2006) 17-24
142. 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 23 5 (2007) 1005-1014
143. 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 3 5 (2007) 495-504
144. Roth T., Seiden D., Sainati S., et al. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med 7 4 (2006) 312-318
145. Johnson M.W., Suess P.E., and Griffiths R.R. Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry 63 10 (2006) 1149-1157
146. Kryger M., Wang-Weigand S., and Roth T. Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea. Sleep Breath 11 3 (2007) 159-164
147. 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 13 1 (2009) 79-84
148. 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 12 3 (2008) 243-250
149. 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 306 3 (2003) 954-964
150. Turek F.W., and Gillette M.U. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med 5 6 (2004) 523-532
151. 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) 63 3 (2005) 298-304
152. Boivin D.B. Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders. J Psychiatry Neurosci 25 5 (2000) 446-458
153. 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 18 3 (1990) 199-210
154. Dalton E.J., Rotondi D., Levitan R.D., et al. Use of slow-release melatonin in treatment-resistant depression. J Psychiatry Neurosci 25 1 (2000) 48-52
155. Zupancic M., and Guilleminault C. Agomelatine: a preliminary review of a new antidepressant. CNS Drugs 20 12 (2006) 981-992
156. Pandi-Perumal S.R., Srinivasan V., Maestroni G.J., et al. Melatonin: nature's most versatile biological signal?. FEBS J 273 13 (2006) 2813-2838
157. Loo H., Hale A., and 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 17 5 (2002) 239-247
158. Kennedy S.H., and Emsley R. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 16 2 (2006) 93-100
159. Olie J.P., and Emsley R. Confirmed clinical efficacy of agomelatine (25-50 mg) in major depression: two randomized, double-blind, placebo-controlled studies. Eur Neuropsychopharmacol 15 Suppl 3 (2005) S416
160. Olie J.P., and Kasper S. Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol 10 5 (2007) 661-673
161. 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 373 9662 (2009) 482-491
162. Vachharajani N.N., Yeleswaram K., and Boulton D.W. Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist. J Pharm Sci 92 4 (2003) 760-772
163. 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 19 5 (2002) 915-936
164. Mulchahey J.J., Goldwater D.R., and 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 75 15 (2004) 1843-1856
165. 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 66 3 (2005) 384-390
166. Maquet P. The role of sleep in learning and memory. Science 294 5544 (2001) 1048-1052
167. Walker M.P., and Stickgold R. Sleep, memory, and plasticity. Annu Rev Psychol 57 (2006) 139-166
168. Graves L., Pack A., and Abel T. Sleep and memory: a molecular perspective. Trends Neurosci 24 4 (2001) 237-243
169. Stickgold R., and Walker M.P. Sleep and memory: the ongoing debate. Sleep 28 10 (2005) 1225-1227
170. 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 102 35 (2005) 12589-12594
171. Dana R.C., and Martinez Jr. J.L. Effect of adrenalectomy on the circadian rhythm of LTP. Brain Res 308 2 (1984) 392-395
172. Chaudhury D., Wang L.M., and Colwell C.S. Circadian regulation of hippocampal long-term potentiation. J Biol Rhythms 20 3 (2005) 225-236
173. Claridge-Chang A., Wijnen H., Naef F., et al. Circadian regulation of gene expression systems in the Drosophila head. Neuron 32 4 (2001) 657-671
174. 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 439 1 (2008) 34-36
175. Imbesi M., Uz T., and Manev H. Melatonin receptor agonist ramelteon activates the extracellular signal-regulated kinase 1/2 in mouse cerebellar granule cells. Neuroscience 155 4 (2008) 1160-1164