Chronobiology of melatonin beyond the feedback to the suprachiasmatic nucleus-consequences to melatonin dysfunction

International Journal of Molecular Sciences

Volumn 14, Issue 3, 2013, Pages 5817-5841

  Hardeland, Rüdiger ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

Age related diseases; Aging; Circadian; Melatonergic agonists; Melatonin; MT1; MT2; Peripheral oscillators; Polymorphisms

Indexed keywords

MELATONIN; MELATONIN 1 RECEPTOR; MELATONIN 2 RECEPTOR; TRANSCRIPTION FACTOR CLOCK;

AGING; CENTRAL NERVOUS SYSTEM; CHRONOBIOLOGY; CIRCADIAN RHYTHM; ENDOCRINE DISEASE; GENE EXPRESSION REGULATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HORMONE ACTION; HORMONE RELEASE; HORMONE SYNTHESIS; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; PERIPHERAL NERVOUS SYSTEM; PINEAL BODY; PROTEIN EXPRESSION; RECEPTOR GENE; REVIEW; SIGNAL TRANSDUCTION; SUPRACHIASMATIC NUCLEUS; TISSUE DISTRIBUTION;

ANIMALIA; MAMMALIA;

EID: 84875554058     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms14035817     Document Type: Review

References (193)

1. Hardeland, R.; Cardinali, D.P.; Srinivasan, V.; Spence, D.W.; Brown, G.M.; Pandi-Perumal, S.R. Melatonin-A pleiotropic, orchestrating regulator molecule. Prog. Neurobiol. 2011, 93, 350-384.
2. Tricoire, H.; Locatelli, A.; Chemineau, P.; Malpaux, B. Melatonin enters the cerebrospinal fluid through the pineal recess. Endocrinology 2002, 143, 84-90.
3. Tricoire, H.; Møller, M.; Chemineau, P.; Malpaux, B. Origin of cerebrospinal fluid melatonin and possible function in the integration of photoperiod. Reprod. Suppl. 2003, 61, 311-321.
4. Stehle, J.H.; von Gall, C.; Korf, H.W. Melatonin: A clock-output, a clock-input. J. Neuroendocrinol. 2003, 15, 383-389.
5. Perreau-Lenz, S.; Kalsbeek, A.; Garidou, M.L.; Wortel, J.; van der Vliet, J.; van Heijningen, C.; Simonneaux, V.; Pévet, P.; Buijs, R.M. Suprachiasmatic control of melatonin synthesis in rats: Inhibitory and stimulatory mechanisms. Eur. J. Neurosci. 2003, 17, 221-228.
6. Hardeland, R. Melatonin, hormone of darkness and more-Occurrence, control mechanisms, actions and bioactive metabolites. Cell Mol. Life Sci. 2008, 65, 2001-2018.
7. Reiter, R.J. Melatonin: The chemical expression of darkness. Mol. Cell Endocrinol. 1991, 79, C153-C159.
8. Reiter, R.J. The melatonin rhythm: Both a clock and a calendar. Experientia 1993, 49, 654-664.
9. Lewy, A.J.; Ahmed, S.; Jackson, J.M.; Sack, R.L. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol. Int. 1992, 9, 380-392.
10. 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.
11. Honma, K.; Honma, S. The SCN-independent clocks, methamphetamine and food restriction. Eur. J. Neurosci. 2009, 30, 1707-1717.
12. Hardeland, R.; Madrid, J.A.; Tan, D.-X.; Reiter, R.J. Melatonin, the circadian multioscillator system and health: The need for detailed analyses of peripheral melatonin signaling. J. Pineal Res. 2012, 52, 139-166.
13. Silver, R.; Schwartz, W.J. The suprachiasmatic nucleus is a functionally heterogeneous timekeeping organ. Methods Enzymol. 2005, 393, 451-465.
14. Belle, M.D.; Diekman, C.O.; Forger, D.B.; Piggins, H.D. Daily electrical silencing in the mammalian circadian clock. Science 2009, 326, 281-284.
15. Zhang, E.E.; Liu, A.C.; Hirota, T.; Miraglia; L.J.; Welch, G.; Pongsawakul, P.Y.; Liu, X.; Atwood, A.; Huss, J.W., 3rd; Janes, J.; et al. A genome-wide RNAi screen for modifiers of the circadian clock in human cells. Cell 2009, 139, 199-210.
16. Zhang, E.E.; Kay, S.A. Clocks not winding down: Unravelling circadian networks. Nat. Rev. Mol. Cell Biol. 2010, 11, 764-776.
17. Yamada, Y.; Forger, D. Multiscale complexity in the mammalian circadian clock. Curr. Opin. Genet. Dev. 2010, 20, 626-633.
18. Wu, T.; Jin, Y.; Ni, Y.; Zhang, D.; Kato, H.; Fu, Z. Effects of light cues on re-entrainment of the food-dominated peripheral clocks in mammals. Gene 2008, 419, 27-34.
19. Wu, T.; Ni, Y.; Zhuge, F.; Fu, Z. Resetting process of peripheral circadian gene expression after the combined reversal of feeding schedule and light/dark cycle via a 24-h light period transition in rats. Physiol. Res. 2010; 59, 581-590.
20. Tosini, G.; Menaker, M. Circadian rhythms in cultured mammalian retina. Science 1996, 272, 419-421.
21. Dinet, V.; Korf, H.W. Impact of melatonin receptors on pCREB and clock-gene protein levels in the murine retina. Cell Tissue Res. 2007, 330, 29-34.
22. Dinet, V.; Ansari, N.; Torres-Farfan, C.; Korf, H.W. Clock gene expression in the retina of melatonin-proficient (C3H) and melatonin-deficient (C57BL) mice. J. Pineal Res. 2007, 42, 83-91.
23. Storch, K.F.; Paz, C.; Signorovitch, J.; Raviola, E.; Pawlyk, B.; Li, T.; Weitz, C.J. Intrinsic circadian clock of the mammalian retina: Importance for retinal processing of visual information. Cell 2007, 130, 730-741.
24. Storch, K.F.; Paz, C.; Signorovitch, J.; Raviola, E.; Pawlyk, B.; Li, T.; Weitz, C.J. Physiological importance of a circadian clock outside the suprachiasmatic nucleus. Cold Spring Harbor Symp. Quant. Biol. 2007, 72, 307-318.
25. Ruan, G.X.; Allen, G.C.; Yamazaki, S.; McMahon, D.G. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA. PLoS Biol. 2008, 6, e249.
26. Tosini, G.; Pozdeyev, N.; Sakamoto, K.; Iuvone, P.M. The circadian clock system in the mammalian retina. Bioessays 2008, 30, 624-633.
27. Ruan, G.X.; Gamble, K.L.; Risner, M.L.; Young, L.A.; McMahon, D.G. Divergent roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillators. PLoS One 2012, 7, e38985.
28. Miñana-Solis, M.C.; Ángeles-Castellanos, M.; Feillet, C.; Pévet, P.; Challet, E.; Escobar, C. Differential effects of a restricted feeding schedule on clock-gene expression in the hypothalamus of the rat. Chronobiol. Int. 2009, 26, 808-820.
29. Bass, J.; Takahashi, J.S. Circadian integration of metabolism and energetics. Science 2010, 330, 1349-1354.
30. Uz, T.; Akhisaroglu, M.; Ahmed, R.; Manev, H. The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice. Neuropsychopharmacology 2003, 28, 2117-2123.
31. Imbesi, M.; Arslan, A.D.; Yildiz, S.; Sharma, R.; Gavin, D.; Tun, N.; Manev, H.; Uz, T. The melatonin receptor MT1 is required for the differential regulatory actions of melatonin on neuronal "clock" gene expression in striatal neurons in vitro. J. Pineal Res. 2009, 46, 87-94.
32. Jilg, A.; Lesny, S.; Peruzki, N.; Schwegler, H.; Selbach, O.; Dehghani, F.; Stehle, J.H. Temporal dynamics of mouse hippocampal clock gene expression support memory processing. Hippocampus 2010, 20, 377-388.
33. Kaneko, K.; Yamada, T.; Tsukita, S.; Takahashi, K.; Ishigaki, Y.; Oka, Y.; Katagiri, H. Obesity alters circadian expressions of molecular clock genes in the brainstem. Brain Res. 2009, 1263, 58-68.
34. Von Gall, C.; Garabette, M.L.; Kell, C.A.; Frenzel, S.; Dehghani, F.; Schumm-Draeger, P.M.; Weaver, D.R.; Korf, H.W.; Hastings, M.H.; Stehle, J.H. Rhythmic gene expression in pituitary depends on heterologous sensitization by the neurohormone melatonin. Nat. Neurosci. 2002, 5, 234-238.
35. Dardente, H.; Menet, J.S.; Poirel, V.J.; Streicher, D.; Gauer, F.; Vivien-Roels, B.; Klosen, P.; Pévet, P.; Masson-Pévet, M. Melatonin induces Cry1 expression in the pars tuberalis of the rat. Brain Res. Mol. Brain Res. 2003, 114, 101-106.
36. Von Gall, C.; Weaver, D.R.; Moek, J.; Jilg, A.; Stehle, J.H.; Korf, H.W. Melatonin plays a crucial role in the regulation of rhythmic clock gene expression in the mouse pars tuberalis. Ann. N.Y. Acad. Sci. 2005, 1040, 508-511.
37. Jilg, A.; Moek, J.; Weaver, D.R.; Korf, H.W.; Stehle, J.H.; von Gall, C. Rhythms in clock proteins in the mouse pars tuberalis depend on MT1 melatonin receptor signalling. Eur. J. Neurosci. 2005, 22, 2845-2854.
38. Johnston, J.D.; Tournier, B.B.; Andersson, H.; Masson-Pévet, M.; Lincoln, G.A.; Hazlerigg, D.G. Multiple effects of melatonin on rhythmic clock gene expression in the mammalian pars tuberalis. Endocrinology 2006, 147, 959-965.
39. Dardente, H. Does a melatonin-dependent circadian oscillator in the pars tuberalis drive prolactin seasonal rhythmicity? J. Neuroendocrinol. 2007, 19, 657-666.
40. Unfried, C.; Burbach, G.; Korf, H.W.; von Gall, C. Melatonin receptor 1-dependent gene expression in the mouse pars tuberalis as revealed by cDNA microarray analysis and in situ hybridization. J. Pineal Res. 2010, 48, 148-156.
41. Bur, I.M.; Zouaoui, S.; Fontanaud, P.; Coutry, N.; Molino, F.; Martin, A.O.; Mollard, P.; Bonnefont, X. The comparison between circadian oscillators in mouse liver and pituitary gland reveals different integration of feeding and light schedules. PLoS One 2010, 5, e15316.
42. Guillaumond, F.; Becquet, D.; Boyer, B.; Bosler, O.; Delaunay, F.; Franc, J.L.; François-Bellan, A.M. DNA microarray analysis and functional profile of pituitary transcriptome under core-clock protein BMAL1 control. Chronobiol. Int. 2012, 29, 103-130.
43. Torres-Farfan, C.; Serón-Ferré, M.; Dinet, V.; Korf, H.W. Immunocytochemical demonstration of day/night changes of clock gene protein levels in the murine adrenal gland: Differences between melatonin-proficient (C3H) and melatonin-deficient (C57BL) mice. J. Pineal Res. 2006, 40, 64-70.
44. Chung, S.; Son, G.H.; Kim, K. Adrenal peripheral oscillator in generating the circadian glucocorticoid rhythm. Ann. N.Y. Acad. Sci. 2011, 1220, 71-81.
45. Chung, S.; Son, G.H.; Kim, K. Circadian rhythm of adrenal glucocorticoid: Its regulation and clinical implications. Biochim. Biophys. Acta 2011, 1812, 581-591.
46. Son, G.H.; Chung, S.; Kim, K. The adrenal peripheral clock: Glucocorticoid and the circadian timing system. Front. Neuroendocrinol. 2011, 32, 451-465.
47. Peschke, E.; Peschke, D. Evidence for a circadian rhythm of insulin release from perifused rat pancreatic islets. Diabetologia 1998, 41, 1085-1092.
48. Mühlbauer, E.; Wolgast, S.; Finckh, U.; Peschke, D.; Peschke, E. Indication of circadian oscillations in the rat pancreas. FEBS Lett. 2004, 564, 91-96.
49. Peschke, E. Melatonin, endocrine pancreas and diabetes. J. Pineal Res. 2008, 44, 26-40.
50. Oishi, K.; Fukui, H.; Ishida, N. Rhythmic expression of BMAL1 mRNA is altered in Clock mutant mice: Differential regulation in the suprachiasmatic nucleus and peripheral tissues. Biochem. Biophys. Res. Commun. 2000, 268, 164-171
51. Stokkan, K.A.; Yamazaki, S.; Tei, H.; Sakaki, Y.; Menaker, M. Entrainment of the circadian clock in the liver by feeding. Science 2001, 291, 490-493.
52. Storch, K.F.; Lipan, O.; Leykin, I.; Viswanathan, N.; Davis, F.C.; Wong, W.H.; Weitz, C.J. Extensive and divergent circadian gene expression in liver and heart. Nature 2002, 417, 78-83.
53. Kornmann, B.; Schaad, O.; Bujard, H.; Takahashi, J.S.; Schibler, U. System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol. 2007, 5, e34.
54. Kornmann, B.; Schaad, O.; Reinke, H.; Saini, C.; Schibler, U. Regulation of circadian gene expression in liver by systemic signals and hepatocyte oscillators. Cold Spring Harb. Symp. Quant. Biol. 2007, 72, 319-330.
55. Lamia, K.A.; Storch, K.F.; Weitz, C.J. Physiological significance of a peripheral tissue circadian clock. Proc. Natl. Acad. Sci. USA 2008, 105, 15172-15177.
56. Hirao, A.; Nagahama, H.; Tsuboi, T.; Hirao, M.; Tahara, Y.; Shibata, S. Combination of starvation interval and food volume determines the phase of liver circadian rhythm in Per2::Luc knock-in mice under two meals per day feeding. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G1045-G1053.
57. Hsieh, M.C.; Yang, S.C.; Tseng, H.L.; Hwang, L.L.; Chen, C.T.; Shieh, K.R. Abnormal expressions of circadian-clock and circadian clock-controlled genes in the livers and kidneys of long-term, high-fat-diet-treated mice. Int. J. Obes. 2010, 34, 227-239.
58. Motosugi, Y.; Ando, H.; Ushijima, K.; Maekawa, T.; Ishikawa, E.; Kumazaki, M.; Fujimura, A. Tissue-dependent alterations of the clock gene expression rhythms in leptin-resistant Zucker diabetic fatty rats. Chronobiol. Int. 2011, 28, 968-972.
59. Mazzoccoli, G.; Francavilla, M.; Pazienza, V.; Benegiamo, G.; Piepoli, A.; Vinciguerra, M.; Giuliani, F.; Yamamoto, T.; Takumi, T. Differential patterns in the periodicity and dynamics of clock gene expression in mouse liver and stomach. Chronobiol. Int. 2012, 29, 1300-1311.
60. Takahashi, K.; Yamada, T.; Tsukita, S.; Kaneko, K.; Shirai, Y.; Munakata, Y.; Ishigaki, Y.; Imai, J.; Uno, K.; Hasegawa, Y.; et al. Chronic mild stress alters circadian expressions of molecular clock genes in the liver. Am. J. Physiol. Endocrinol. Metab. 2013, 304, E301-E309.
61. Gómez-Santos, C.; Gómez-Abellán, P.; Madrid, J.A.; Hernández-Morante, J.J.; Lujan, J.A.; Ordovas, J.M.; Garaulet, M. Circadian rhythm of clock genes in human adipose explants. Obesity 2009, 17, 1481-1485.
62. Young, M.E.; Razeghi, P.; Taegtmeyer, H. Clock genes in the heart: Characterization and attenuation with hypertrophy. Circ. Res. 2001, 88, 1142-1150.
63. Young, M.E.; Wilson, C.R.; Razeghi, P.; Guthrie, P.H.; Taegtmeyer, H. Alterations of the circadian clock in the heart by streptozotocin-induced diabetes. J. Mol. Cell Cardiol. 2002, 34, 223-231.
64. Jeyaraj, D.; Haldar, S.M.; Wan, X.; McCauley, M.D.; Ripperger, J.A.; Hu, K.; Lu, Y.; Eapen, B.L.; Sharma, N.; Ficker, E.; et al. Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature 2012, 483, 96-99.
65. Zeman, M.; Herichová, I. Melatonin and clock genes expression in the cardiovascular system. Front. Biosci. 2013, 5, 743-753.
66. Kennaway, D.J.; Varcoe, T.J.; Mau, V.J. Rhythmic expression of clock and clock-controlled genes in the rat oviduct. Mol. Hum. Reprod. 2003, 9, 503-507.
67. Fu, L.; Patel, M.S.; Bradley, A.; Wagner, E.F.; Karsenty, G. The molecular clock mediates leptin-regulated bone formation. Cell 2005, 122, 803-815.
68. Fu, L.; Patel, M.S.; Karsenty, G. The circadian modulation of leptin-controlled bone formation. Prog. Brain Res. 2006, 153, 177-188.
69. Yagita, K.; Tamanini, F.; van Der Horst, G.T.; Okamura, H. Molecular mechanisms of the biological clock in cultured fibroblasts. Science 2001, 292, 278-281.
70. Welsh, D.K.; Yoo, S.H.; Liu, A.C.; Takahashi, J.S.; Kay, S.A. Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression. Curr. Biol. 2004, 14, 2289-2295.
71. Hardeland, R.; Coto-Montes, A.; Poeggeler, B. Circadian rhythms, oxidative stress and antioxidative defense mechanisms. Chronobiol. Int. 2003, 20, 921-962.
72. Hardeland, R. Antioxidative protection by melatonin-Multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 2005, 27, 119-130.
73. Baydas, G.; Gursu, M.F.; Yilmaz, S.; Canpolat, S.; Yasar, A.; Cikim, G.; Canatan H. Daily rhythms of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats. Neurosci. Lett. 2002, 323, 195-198.
74. Pablos, M.I.; Reiter, R.J.; Ortiz, G.G.; Guerrero, J.M.; Agapito, M.T.; Chuang, J.I.; Sewerynek, E. Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light. Neurochem. Int. 1998, 32, 69-75.
75. Reiter, R.J.; Tan, D.-X.; Mayo, J.C.; Sainz, R.M.; Leon, J.; Czarnocki, Z. Melatonin as an antioxidant: Biochemical mechanisms and pathophysiological implications in humans. Acta Biochim. Pol. 2003, 50, 1129-1146.
76. Pandi-Perumal, S.R.; Srinivasan, V.; Maestroni, G.J.M.; Cardinali, D.P.; Poeggeler, B.; Hardeland, R. Melatonin: Nature's most versatile biological signal? FEBS J. 2006, 273, 2813-2838.
77. Hardeland, R.; Poeggeler, B. Melatonin beyond its classical functions. Open Physiol. J. 2008, 1, 1-23.
78. Hardeland, R. Diurnal variations in inducibility of hepatic tyrosine aminotransferase. Int. J. Biochem. 1973, 4, 357-364.
79. Morris, J.E.; Peraino, C. Immunochemical studies of serine dehydratase and ornithine aminotransferase regulation in rat liver in vivo. J. Biol. Chem. 1976, 251, 2571-2578.
80. Peraino, C.; Morris, J.E.; Shenoy, S.T. Evidence for different mechanisms in the circadian and glucocorticoid control of rat liver ornithine aminotransferase synthesis. Life Sci. 1976, 19, 1435-1437.
81. Kiessling, S.; Eichele, G.; Oster, H. Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag. J. Clin. Invest. 2010, 120, 2600-2609.
82. Balsalobre, A.; Brown, S.A.; Marcacci, L.; Tronche, F.; Kellendonk, C.; Reichardt, H.M.; Schütz, G.; Schibler, U. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 2000, 289, 2344-2347.
83. Noguchi, T.; Ikeda, M.; Ohmiya, Y.; Nakajima, Y. A dual-color luciferase assay system reveals circadian resetting of cultured fibroblasts by co-cultured adrenal glands. PLoS One 2012, 7, e37093.
84. Wu, X.; Yu, G.; Parks, H.; Hebert, T.; Goh B.C.; Dietrich, M.A.; Pelled, G.; Izadpanah, R.; Gazit, D.; Bunnell, B.A.; et al. Circadian mechanisms in murine and human bone marrow mesenchymal stem cells following dexamethasone exposure. Bone 2008, 42, 861-870.
85. Le Minh, N.; Damiola, F.; Tronche, F.; Schütz, G.; Schibler, U. Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators. EMBO J. 2001, 20, 7128-7136.
86. Gibbs, J.E.; Beesley, S.; Plumb, J.; Singh, D.; Farrow, S.; Ray, D.W.; Loudon, A.S. Circadian timing in the lung; a specifoc role for bronchiolar epithelial cells. Endocrinology 2009, 150, 268-276.
87. Torres-Farfan, C.; Richter, H.G.; Rojas-García, P.; Vergara, M.; Forcelledo, M.L.; Valladares, L.E.; Torrealba, F.; Valenzuela, G.J.; Serón-Ferré, M. mt1 Melatonin receptor in the primate adrenal gland: Inhibition of adrenocorticotropin-stimulated cortisol production by melatonin. J. Clin. Endocrinol. Metab. 2003, 88, 450-458.
88. Doyle, S.E.; Grace, M.S.; McIvor, W.; Menaker, M. Circadian rhythms of dopamine in mouse retina: The role of melatonin. Vis. Neurosci. 2002, 19, 593-601.
89. Pozdeyev, N.; Tosini, G.; Li, L.; Ali, F.; Rozov, S.; Lee, R.H.; Iuvone, P.M. Dopamine modulates diurnal and circadian rhythms of protein phosphorylation in photoreceptor cells of mouse retina. Eur. J. Neurosci. 2008, 27, 2691-2700.
90. Iuvone, P.M.; Tosini, G.; Pozdeyev, N.; Haque, R.; Klein, D.C.; Chaurasia, S.S. Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Prog. Retin. Eye Res. 2005, 24, 433-456.
91. Coon, S.L.; del Olmo, E.; Young, W.S., 3rd; Klein, D.C. Melatonin synthesis enzymes in Macaca mulatta: Focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87). J. Clin. Endocrinol. Metab. 2002, 87, 4699-4706.
92. Klein, D.C. Arylalkylamine N-acetyltransferase: "The timezyme". J. Biol. Chem. 2007, 282, 4233-4237.
93. Mühlbauer, E.; Gross, E.; Labucay, K.; Wolgast, S.; Peschke, E. Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose. Eur. J. Pharmacol. 2009, 606, 61-71.
94. Tanioka, M.; Yamada, H.; Doi, M.; Bando, H.; Yamaguchi, Y.; Nishigori, Y.; Okamura, H. Molecular clocks in mouse skin. J. Invest. Dermatol. 2009, 129, 1225-1231.
95. Akashi, M.; Soma, H.; Yamamoto, T.; Tsugitomi, A.; Yamashita, S.; Yamamoto, T.; Nishida, E.; Yasuda, A.; Liao, J.K.; Node, K. Noninvasive method for assessing the human circadian clock using hair follicle cells. Proc. Natl. Acad. Sci. USA 2010, 107, 15643-15648.
96. Watanabe, M.; Hida, A.; Kitamura, S.; Enomoto, M.; Ohsawa, Y.; Katayose, Y.; Nozaki, K.; Moriguchi, Y.; Anitake, S.; Higuchi, S.; et al. Rhythmic expression of circadian clock genes in human leukocytes and beard hair follicle cells. Biochem. Biophys. Res. Commun. 2012, 425, 902-907.
97. Slominski, A.; Wortsman, J.; Tobin, D.J. The cutaneous serotoninergic/melatoninergic system: Securing a place under the sun. FASEB J. 2005, 19, 176-194.
98. Slominski, A.; Wortsman, J.; Tuckey, R.C.; Paus, R. Differential expression of HPA axis homolog in the skin. Mol. Cell Endocrinol. 2007, 265-266, 143-149.
99. Slominski, A.T.; Zmijewski, M.A.; Skobowiat, C.; Zbytek, B.; Slominski, R.M.; Steketee, J.D. Sensing the environment: Regulation of local and global homeostasis by the skin neuroendocrine system. Adv. Anat. Embryol. Cell Biol. 2012, 212, 1-115.
100. Deacon, S.; Arendt, J. Melatonin-induced temperature suppression and its acute phase-shifting effects correlated in a dose-dependent manner in humans. Brain Res. 1995, 688, 77-85.
101. 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.
102. Cajochen, C.; Kräuchi, K.; Wirz-Justice, A. Role of melatonin in the regulation of human circadian rhythms and sleep. J. Neuroendocrinol. 2003, 15, 432-437.
103. Gubin, D.G.; Gubin, G.D.; Waterhouse, J.; Weinert, D. The circadian body temperature rhythm in the elderly: Effect of single daily melatonin dosing. Chronobiol. Int. 2006, 23, 639-658.
104. Buhr, E.D.; Yoo, S.H.; Takahashi, J.S. Temperature as a universal resetting cue for mammalian circadian oscillators. Science 2010, 330, 379-385.
105. Brown, S.A.; Zumbrunn, G.; Fleury-Olela, F.; Preitner, N.; Schibler, U. Rhythms of mammalian body temperature can sustain peripheral circadian clocks. Curr. Biol. 2002, 12, 1574-1583.
106. Saini, C.; Morf, J.; Stratmann, M.; Gos, P. Schibler, U. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators. Genes Dev. 2012, 26, 567-580.
107. Weinert, D. Circadian temperatue variation and ageing. Aging Res. Rev. 2010, 9, 51-60.
108. Soria, V.; Martínez-Amorós, E.; Escaramís, G.; Valero, J.; Crespo, J.M.; Gutiérrez-Zotes, A.; Bayés, M.; Martorell, L.; Vilella, E.; Estivill, X.; et al. Resequencing and association analysis of arylalkylamine N-acetyltransferase (AANAT) gene and its contribution to major depression susceptibility. J. Pineal Res. 2010, 49, 35-44.
109. Goubran Botros, H.; Legrand, P.; Pagan, C.; Bondet, V.; Weber, P.; Ben-Abdallah, M.; Lemière, N.; Huguet, G.; Bellalou, J.; Maronde, E.; et al. Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. J. Pineal Res. 2013, 54, 46-57.
110. Toma, C.; Rossi, M.; Sousa, I.; Blasi, F.; Bacchelli, E.; Alen, R.; Vanhala, R.; Monaco, A.P.; Järvelä, I.; Maestrini, E.; International Molecular Genetic Study of Autism Consortium. Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations. Mol. Psychiatr. 2007, 12, 977-999.
111. Melke, J.; Goubran Botros, H.; Chaste, P.; Betancur, C.; Nygren, G.; Anckarsäter, H.; Rastam, M.; Ståhlberg, O.; Gillberg, I.C.; Delorme, R.; et al. Abnormal melatonin synthesis in autism spectrum disorders. Mol. Psychiatr. 2008, 13, 90-98.
112. Jonsson, L.; Ljunggren, E.; Bremer, A.; Pedersen, C.; Landén, M.; Thuresson, K.; Giacobini, M.; Melke, J. Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC Med. Genomics 2010, 3, 10.
113. Chaste, P.; Clement, N.; Botros, H.G.; Guillaume, J.L.; Konyukh, M.; Pagan, C.; Scheid, I.; Nygren, G.; Anckarsäter, H.; Rastam, M.; et al. Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders. J. Pineal Res. 2011, 51, 394-399.
114. Gałecki, P.; Szemraj, J.; Bartosz, G.; Bieńkiewicz, M.; Gałecka, E.; Florkowski, A.; Lewiński, A.; Karbownik-Lewińska, M. Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. J. Pineal Res. 2010, 48, 311-317.
115. Etain, B.; Dumaine, A.; Bellivier, F.; Pagan, C.; Francelle, L.; Goubran-Botros, H.; Moreno, S.; Deshommes, J.; Moustafa, K.; le Dudal, K.; et al. Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder. Hum. Mol. Genet. 2012, 21, 4030-4037.
116. Park, H.J.; Park, J.K.; Kim, S.K.; Cho, A.R.; Kim, J.W.; Yim, S.V.; Chung, J.H. Association of polymorphism in the promoter of the melatonin receptor 1A gene with schizophrenia and with insomnia symptoms in schizophrenia patients. J. Mol. Neurosci. 2011, 45, 304-308.
117. Samimi-Fard, S.; Abreu-Gonzalez, P.; Dominguez-Rodriguez, A.; Jimenez-Sosa, A. A case-Control study of melatonin receptor type 1A polymorphism and acute myocardial infarction in a Spanish population. J. Pineal Res. 2011, 51, 400-404.
118. Li, C.; Shi, Y.; You, L.; Wang, L.; Chen, Z.J. Melatonin receptor 1A gene polymorphism associated with polycystic ovary syndrome. Gynecol. Obstet. Invest. 2011, 72, 130-134.
119. Esposito, T.; Rendina, D.; Aloia, A.; Formicola, D.; Magliocca, S.; de Filippo, G.; Muscariello, R.; Mossetti, G.; Gianfrancesco, F.; Strazzullo, P. The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis. Nephrol. Dial. Transplant. 2012, 27, 210-218.
120. Li, C.; Shi, Y.; You, L.; Wang, L.; Chen, Z.J. Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome. Mol. Hum. Reprod. 2011, 17, 193-198.
121. Ha, E.; Choe, B.K.; Jung, K.H.; Yoon, S.H.; Park, H.J.; Park, H.K.; Yim, S.V.; Chung, J.H.; Bae, H.S.; Nam, M.; et al. Positive relationship between melatonin receptor type 1B polymorphism and rheumatoid factor in rheumatoid arthritis patients in the Korean population. J. Pineal Res. 2005, 39, 201-205.
122. Natarajan, R.; Einarsdottir, E.; Riutta, A.; Hagman, S.; Raunio, M.; Mononen, N.; Lehtimäki, T.; Elovaara, I. Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients. J. Neuroimmunol. 2012, 250, 106-110.
123. Qiu, X.S.; Tang, N.L.; Yeung, H.Y.; Lee, K.M.; Hung, V.W.; Ng, B.K.; Ma, S.L.; Kwok, R.H.; Qin, L.; Qiu, Y.; et al. Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine 2007, 32, 1748-1753.
124. Mórocz, M.; Czibula, A.; Grózer, Z.B.; Szécsényi, A.; Almos, P.Z.; Raskó, I.; Illés, T. Association study of BM. P4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. Spine 2011, 36, E123-E130.
125. Hardeland, R. Melatonin in aging and disease-Multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. 2012, 3, 194-225.
126. Dufourny, L.; Levasseur, A.; Migaud, M.; Callebaut, I.; Pontarotti, P.; Malpaux, B.; Monget, P. GPR50 is the mammalian ortholog of Mel1c: Evidence of rapid evolution in mammals. BMC Evol. Biol. 2008, 8, 105.
127. 1 melatonin receptor function through heterodimerization. EMBO J. 2006, 25, 3012-3023.
128. 2 receptor agonist. Neuropharmacology 2005, 48, 301-310.
129. Sack, R.L.; Lewy, A.J.; Erb, D.L.; Vollmer, W.M.; Singer, C.M. Human melatonin production decreases with age. J. Pineal Res. 1986, 3, 379-388.
130. Karasek, M.; Reiter, R.J. Melatonin and aging. Neuroendocrinol. Lett. 2002, 23, 14-16.
131. Skene, D.J.; Swaab, D.F. Melatonin rhythmicity: Effect of age and Alzheimer's disease. Exp. Gerontol. 2003, 38, 199-206.
132. Cardinali, D.P.; Esquifino, A.I.; Srinivasan, V.; Pandi-Perumal, S.R. Melatonin and the immune system in aging. Neuroimmunomodulation 2008, 15, 272-278.
133. Srinivasan, V.; Pandi-Perumal, S.R.; Maestroni, G.J.M.; Esquifino, A.I.; Hardeland, R.; Cardinali, D.P. Role of melatonin in neurodegenerative diseases. Neurotox. Res. 2005, 7, 293-318.
134. Wu, Y.H.; Fischer, D.F.; Kalsbeek, A.; Garidou-Boof, M.L.; van der Vliet, J.; van Heijningen, C.; Liu, R.Y.; Zhou, J.N.; Swaab, D.F. Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the "master clock". FASEB J. 2006, 20, 1874-1876.
135. Wu, Y.H.; Swaab, D.F. Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease. Sleep Med. 2007, 8, 623-636.
136. Schmid, H. A Decreased melatonin biosynthesis, calcium flux, pineal gland calcification and aging: A hypothetical framework. Gerontology 1993, 39, 189-199.
137. Kunz, D.; Schmitz, S.; Mahlberg, R.; Mohr, A.; Stoter, C.; Wolf, K.J.; Herrmann, W.M. A new concept for melatonin deficit: On pineal calcification and melatonin excretion. Neuropsychopharmacology 1999, 21, 765-772.
138. Skene, D.J.; Vivien-Roels, B.; Sparks, D.L.; Hunsaker, J.C.; Pévet, P.; Ravid, D.; Swaab, D.F. Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: Effect of age and Alzheimer's disease. Brain Res. 1990, 528, 170-174.
139. Uchida, K.; Okamoto, N.; Ohara, K.; Morita, Y. Daily rhythm of serum melatonin in patients with dementia of the degenerate type. Brain Res. 1996, 717, 154-159.
140. Liu, R.Y.; Zhou, J.N.; van Heerikhuize, J.; Hofman, M.A.; Swaab, D.F. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-ε4/4 genotype. J. Clin. Endocrinol. Metab. 1999, 84, 323-327.
141. Mishima, K.; Tozawa, T.; Satoh, K.; Matsumoto, Y.; Hishikawa, Y.; Okawa, M. Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking. Biol. Psychiatr. 1999, 45, 417-421.
142. Ohashi, Y.; Okamoto, N.; Uchida, K.; Iyo, M.; Mori, N.; Morita, Y. Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type. Biol. Psychiatr. 1999, 45, 1646-1652.
143. Ferrari, E.; Fioravanti, M.; Magri, F.; Solerte, S.B. Variability of interactions between neuroendocrine and immunological functions in physiological aging and dementia of the Alzheimer's type. Ann. N.Y. Acad. Sci. 2000, 917, 582-596.
144. Rosen, R.; Hu, D.N.; Perez, V.; Tai, K.; Yum G.P.; Chen, M.; Tone, P.; McCormick, S.A.; Walsh, J. Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients. Mol. Vis. 2009, 15, 673-679.
145. Monteleone, P.; Maj, M.; Fusco, M.; Kemali, D.; Reiter, R.J. Depressed nocturnal plasma melatonin levels in drug-free paranoid schizophrenics. Schizophr. Res. 1992, 7, 77-84.
146. Viganò, D.; Lissoni, P.; Rovelli, F.; Roselli, M.G.; Malugani, F.; Gavazzeni, C.; Conti, A.; Maestroni, G. A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. Neuroendocrinol. Lett. 2001, 22, 137-141.
147. Catapano, F.; Monteleone, P.; Fuschino, A.; Maj, M.; Kemali, D. Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Psychiatr. Res. 1992, 44, 217-225.
148. Akpinar, Z.; Tokgöz, S.; Gökbel, H.; Okudan, N.; Uǧuz, F.; Yilmaz, G. The association of nocturnal serum melatonin levels with major depression in patients with acute multiple sclerosis. Psychiatr. Res. 2008, 161, 253-257.
149. Brugger, P.; Marktl, W.; Herold, M. Impaired nocturnal secretion of melatonin in coronary heart disease. Lancet 1995, 345, 1408.
150. Girotti, L.; Lago, M.; Ianovsky, O.; Carbajales, J.; Elizari, M.V.; Brusco, L.I.; Cardinali, D.P. Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease. J. Pineal Res. 2000, 29, 38-42.
151. Sewerynek, E. Melatonin and the cardiovascular system. Neuroendocrinol. Lett. 2002, 23, 79-83.
152. Altun, A.; Yaprak, M.; Aktoz, M.; Vardar, A.; Betul, U.A.; Ozbay, G. Impaired nocturnal synthesis of melatonin in patients with cardiac syndrome X. Neurosci. Lett. 2002, 327, 143-145.
153. Yaprak, M.; Altun, A.; Vardar, A.; Aktoz, M.; Ciftci, S.; Ozbay, G. Decreased nocturnal synthesis of melatonin in patients with coronary artery disease. Int. J. Cardiol. 2003, 89, 103-107.
154. Dominguez-Rodriguez, A.; Abreu-Gonzalez, P.; Garcia-Gonzalez, M.J.; Samimi-Fard, S.; Kaski, J.C.; Reiter. R.J. Light/dark patterns of soluble vascular cell adhesion molecule-1 in relation to melatonin in patients with ST-segment elevation myocardial infarction. J. Pineal Res. 2008, 44, 65-69.
155. Dominguez-Rodriguez, A.; Abreu-Gonzalez, P.; Reiter, R.J. Clinical aspects of melatonin in the acute coronary syndrome. Curr. Vasc. Pharmacol. 2009, 7, 367-373.
156. Rohr, U.D.; Herold, J. Melatonin deficiencies in women. Maturitas 2002, 41, S85-S104.
157. Claustrat, B.; Loisy, C.; Brun, J.; Beorchia, S.; Arnaud, J.L.; Chazot, G. Nocturnal plasma melatonin levels in migraine: A preliminary report. Headache 1989, 29, 242-245.
158. Claustrat, B.; Brun, J.; Geoffriau, M.; Zaidan, R.; Mallo, C.; Chazot, G. Nocturnal plasma melatonin profile and melatonin kinetics during infusion in status migrainosus. Cephalalgia 1997, 17, 511-517.
159. Bazil, C.W.; Short, D.; Crispin, D.; Zheng, W. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology 2000, 55, 1746-1748.
160. Uberos, J.; Augustin-Morales, M.C.; Molina Carballo, A.; Florido, J.; Narbona, E.; Muñoz-Hoyos, A. Normalization of the sleep-wake pattern and melatonin and 6-sulphatoxy-melatonin levels after a therapeutic trial with melatonin in children with severe epilepsy. J. Pineal Res. 2011, 50, 192-196.
161. Aoki, M.; Yokota, Y.; Hayashi, T.; Kuze, B.; Murai, M.; Mizuta, K.; Ito, Y. Disorder of the saliva melatonin circadian rhythm in patients with Meniere's disease. Acta Neurol. Scand. 2006, 113, 256-261.
162. Perras, B.; Kurowski, V.; Dodt, C. Nocturnal melatonin concentration is correlated with illness severity in patients with septic disease. Intensive Care Med. 2006, 32, 624-625.
163. Perras, B.; Meier, M.; Dodt, C. Light and darkness fail to regulate melatonin release in critically ill humans. Intensive Care Med. 2007, 33, 1954-1958.
164. Srinivasan, V.; Pandi-Perumal, S.R.; Spence, D.W.; Kato, H.; Cardinali, D.P. Melatonin in septic shock: Some recent concepts. J. Crit. Care 2010, 25, 656. e1-656. e6.
165. Shigeta, H.; Yasui, A.; Nimura, Y.; Machida, N.; Kageyama, M.; Miura, M.; Menjo, M.; Ikeda, K. Postoperative delirium and melatonin levels in elderly patients. Am. J. Surg. 2001, 182, 449-454.
166. Puy, H.; Deybach, J.C.; Baudry, P.; Callebert, J.; Touitou, Y.; Nordmann, Y. Decreased nocturnal plasma melatonin levels in patients with recurrent acute intermittent porphyria attacks. Life Sci. 1992, 53, 621-627.
167. Bylesjö, I.; Forsgren, L.; Wetterberg, L. Melatonin and epileptic seizures in patients with acute intermittent porphyria. Epileptic Disord. 2000, 2, 203-208.
168. Grin, W.; Grünberger, W. A significant correlation between melatonin deficiency and endometrial cancer. Gynecol. Obstet. Invest. 1998, 45, 62-65.
169. Hu, S.; Shen, G.; Yin, S.; Xu, W.; Hu, B. Melatonin and tryptophan circadian profiles in patients with advanced non-small cell lung cancer. Adv. Ther. 2009, 26, 886-892.
170. O'Brien, I.A.; Lewin, I.G.; O'Hare, J.P.; Arendt, J.; Corrall, R.J. Abnormal circadian rhythm of melatonin in diabetic autonomic neuropathy. Clin. Endocrinol. 1986, 24, 359-364.
171. Peschke, E.; Stumpf, I.; Bazwinsky, I.; Litvak, L.; Dralle, H.; Mühlbauer, E. Melatonin and type 2 diabetes-A possible link? J. Pineal Res. 2007, 42, 350-358.
172. Jan, J.E.; Reiter, R.J.; Wasdell, M.B.; Bax, M. The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders. J. Pineal Res. 2009, 46, 1-7.
173. Hardeland, R. New approaches in the management of insomnia: Weighing the advantages of prolonged release melatonin and synthetic melatoninergic agonists. Neuropsychiatr. Dis. Treat. 2009, 5, 341-354.
174. Singer, C.; Tractenberg, R.E.; Kaye, J.; Schafer, K.; Gamst, A.; Grundman, M.; Thomas, R.; Thal, L.J. Alzheimer's disease cooperative study. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep 2003, 26, 893-901.
175. McCurry, S.M.; Reynolds, C.F.; Ancoli-Israel, S.; Teri, L.; Vitiello, M.V. Treatment of sleep disturbance in Alzheimer's disease. Sleep Med. Rev. 2000, 4, 603-628.
176. Cardinali, D.P.; Brusco, L.I.; Liberczuk, C.; Furio, A.M. The use of melatonin in Alzheimer's disease. Neuroendocrinol. Lett. 2002, 23, 20-23.
177. Srinivasan, V.; Pandi-Perumal, S.R.; Cardinali, D.P.; Poeggeler, B.; Hardeland, R. Melatonin in Alzheimer's disease and other neurodegenerative disorders. Behav. Brain Funct. 2006, 2, 15.
178. Hardeland, R. Melatonin: Signaling mechanisms of a pleiotropic agent. BioFactors 2009, 35, 183-192.
179. 2 melatonin receptors in mammals. Endocrine 2005, 27, 101-110.
180. Ebisawa, T.; Kajimura, N.; Uchiyama, M.; Katoh, M.; Sekimoto, M.; Watanabe, T.; Ozeki, Y.; Ikeda, M.; Jodoi, T.; Sugishita, M.; et al. Alleic variants of human melatonin 1a receptor: Function and prevalence in subjects with circadian rhythm sleep disorders. Biochem. Biophys. Res. Commun. 1999, 262, 832-837.
181. Bonnefond, A.; Clément, N.; Fawcett, K.; Yengo, L.; Vaillant, E.; Guillaume, J.L.; Dechaume, A.; Payne, F.; Roussel, R.; Czernichow, S.; et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat. Genet. 2012, 44, 297-301.
182. Nagorny, C.; Lyssenko, V. Tired of diabetes genetics? Circadian rhythms and diabetes: The MTNR1B story? Curr. Diab. Rep. 2012, 12, 667-672.
183. Claustrat, B.; Brun, J.; Chazot, G. The basic physiology and pathophysiology of melatonin. Sleep Med. Rev. 2005, 9, 11-24.
184. Hardeland, R.; Poeggeler, B.; Srinivasan, V.; Trakht, I.; Pandi-Perumal, S.R.; Cardinali, D.P. Melatonergic drugs in clinical practice. Arzneimittelforschung 2008, 58, 1-10.
185. Srinivasan, V.; Pandi-Perumal, S.R.; Trahkt, I.; Spence, D.W.; Poeggeler, B.; Hardeland, R.; Cardinali, D.P. Melatonin and melatonergic drugs on sleep: Possible mechanisms of action. Int. J. Neurosci. 2009, 119, 821-846.
186. Hardeland, R. Neurobiology, pathophysiology, and treatment of melatonin deficiency and dysfunction. ScientificWorldJournal 2012, 2012, 640389.
187. Hardeland, R.; Poeggeler, B. Melatonin and synthetic melatonergic agonists: Actions and metabolism in the central nervous system. Cent. Nerv. Syst. Agents Med. Chem. 2012, 12, 189-216.
188. Mulchahey, J.J.; Goldwater, D.R.; Zemlan, F.P. A single blind, placebo controlled, across groups dose escalation study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the melatonin analog β-methyl-6-chloromelatonin. Life Sci. 2004, 75, 1843-1856.
189. Bourin, M.; Mocaër, E.; Porsolt, R. Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: Involvement of melatonin and serotonin receptors. J. Psychiatr. Neurosci. 2004, 29, 126-133.
190. 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 the treatment of insomnia. J. Clin. Pharmacol. 2006, 46, 140-148.
191. Pandi-Perumal, S.R.; Srinivasan, V.; Poeggeler, B.; Hardeland, R.; Cardinali, D.P. Drug insight: The use of melatonergic agonists for the treatment of insomnia-Focus on ramelteon. Nat. Clin. Pract. Neurol. 2007, 3, 221-228.
192. Rivara, S.; Mor, M.; Bedini, A.; Spadoni, G.; Tarzia, G. Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr. Top. Med. Chem. 2008, 8, 954-968.
193. Hardeland, R. Investigational melatonin receptor agonists. Expert Opin. Investig. Drugs 2010, 19, 747-764.