Melatonin and synthetic melatoninergic agonists in psychiatric and age-associated disorders: Successful and unsuccessful approaches

Current Pharmaceutical Design

Volumn 22, Issue 8, 2016, Pages 1086-1101

  Hardeland, Rüdiger ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

Agomelatine; Alzheimer s disease; Melatonin; Parkinson s disease; Ramelteon; Sleep; Tasimelteon; TIK 301

Indexed keywords

AGOMELATINE; AH 001; AH 017; GG 012; GR 196429; MA 2; MELATONIN; MELATONIN RECEPTOR AGONIST; PIROMELATINE; RAMELTEON; SEROTONIN ANTAGONIST; TASIMELTEON; TIK 301; UCM 765; UCM 924; UNCLASSIFIED DRUG; ACETAMIDE DERIVATIVE; INDOLE DERIVATIVE; MELATONIN RECEPTOR; N-(2-(5-METHOXY-INDOL-3-YL)-ETHYL)-4-OXO-4H-PYRAN-2-CARBOXAMIDE; PYRAN DERIVATIVE;

AGING; ANTIDEPRESSANT ACTIVITY; ARTICLE; CIRCADIAN RHYTHM; DRUG EFFECT; DRUG HALF LIFE; DRUG METABOLISM; HUMAN; MENTAL DISEASE; PRIORITY JOURNAL; RECEPTOR AFFINITY; SIGNAL TRANSDUCTION; AGONISTS; ANIMAL; MEMORY DISORDERS; MENTAL DISORDERS;

ACETAMIDES; ANIMALS; HUMANS; INDOLES; MELATONIN; MEMORY DISORDERS; MENTAL DISORDERS; PYRANS; RECEPTORS, MELATONIN;

EID: 84960076209     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612822666151214125543     Document Type: Article

References (176)

1. Hardeland R, Cardinali DP, Srinivasan V, et al. Melatonin-A pleiotropic, orchestrating regulator molecule. Prog Neurobiol 2011; 93: 350-84.
2. Acuña-Castroviejo D, Escames G, Venegas C, et al. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 2014; 71: 2997-3025.
3. Hardeland R, Madrid JA, Tan D-X, et al. Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling. J Pineal Res 2012; 52: 139-66.
4. Hardeland R. Chronobiology of melatonin beyond the feedback to the suprachiasmatic nucleus-Consequences to melatonin dysfunction. Int J Mol Sci 2013, 14: 5817-41.
5. Hardeland R. Melatonin and circadian oscillators in aging-A dynamic approach to the multiply connected players. Interdisc Top Gerontol 2015; 40: 128-40.
6. Hardeland R. Neurobiology, pathophysiology, and treatment of melatonin deficiency and dysfunction. ScientificWorldJournal 2012; 2012: 640389.
7. Hardeland, R. Melatonin in aging and disease multiple consequences of reduced secretion, options and limits of treatment. Aging Dis 2012; 3: 194-225.
8. Hardeland R. Melatonin and the theories of aging: a critical appraisal of melatonin's role in antiaging mechanisms. J Pineal Res 2013; 55: 325-356.
9. Hardeland R. Deviations of melatonin levels and signaling in aging and diseases-Options and limits of treatment. In: Srinivasan V, Gobbi G, Shillcutt SD, Suzen S, Eds. Melatonin: Therapeutic Value and Neuroprotection. Boca Raton: CRC Press 2014; pp. 11-8.
10. Perlis ML, Giles DE, Buysse DJ, et al. Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord 1997; 42: 209-12.
11. Pandi-Perumal SR, Trakht I, Srinivasan V, et al. The effect of melatonergic and non-melatonergic antidepressants on sleep: weighing the alternatives. World J Biol Psychiatry 2009; 10: 342-54.
12. Srinivasan V, Pandi-Perumal SR, Trakht I, et al. Pathophysiology of depression: role of sleep and the melatonergic system. Psychiatry Res 2009; 165: 201-14.
13. Aschoff J, Wever R. Human circadian rhythms: a multioscillatory system. Fed Proc 1976; 35: 2326-32.
14. Reinberg AE, Ashkenazi I, Smolensky MH. Euchronism, allochronism, and dyschronism: is internal desynchronization of human circadian rhythms a sign of illness? Chronobiol Int 2007; 24: 553-88.
15. Pandi-Perumal SR, Srinivasan V, Poeggeler B, et al. Drug Insight: the use of melatonergic agonists for the treatment of insomnia-focus on ramelteon. Nat Clin Pract Neurol 2007; 3: 221-8.
16. 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: 341-54.
17. Hardeland R. Investigational melatonin receptor agonists. Expert Opin Investig Drugs 2010; 19: 747-764.
18. EMEA. Assessment report for Circadin. 2007; 52 p. Available from: http.//www. emea. europe. eu/humandocs/PDFs/EPAR/Circadin/H-695-eu6. pdf.
19. Srinivasan V, Brzezinski A, Spence DW, et al. Sleep, mood disorders and antidepressants: the melatonergic antidepressant agomelatine offers a new strategy for treatment. Psychiatr Fenn 2010; 41: 168-87.
20. Hardeland R. Rationale and problems of melatonergic treatment. J Endocrinol Reprod 2012; 16: 7-14.
21. Skene DJ, Vivien-Roels B, Sparks DL, et al. 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: 170-4.
22. Uchida K, Okamoto N, Ohara K, et al. Daily rhythm of serum melatonin in patients with dementia of the degenerate type. Brain Res 1996; 717: 154-9.
23. Mishima K, Tozawa T, Satoh K, et al. Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking. Biol Psychiatry 1999; 45: 417-21.
24. Ohashi Y, Okamoto N, Uchida K, et al. Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type. Biol Psychiatry 1999; 45: 1646-52.
25. Skene DJ, Swaab DF. Melatonin rhythmicity: effect of age and Alzheimer's disease. Exp Gerontol 2003; 38: 199-206.
26. Karasek M, Reiter RJ. Melatonin and aging. Neuroendocrinol Lett 2002; 23, Suppl 1: 14-6.
27. Karasek M. Melatonin, human aging, and age-related diseases. Exp Gerontol 2004; 39: 1723-9.
28. Bubenik GA, Konturek SJ. Melatonin and aging: prospects for human treatment. J Physiol Pharmacol 2011; 62: 13-9.
29. Hofman MA. The human circadian clock and aging. Chronobiol Int 2000; 17: 245-59.
30. Hofman MA, Swaab DF. Living by the clock: The circadian pacemaker in older people. Ageing Res Rev 2006; 5: 33-51.
31. Srinivasan V, Pandi-Perumal SR, Cardinali DP, et al. Melatonin in Alzheimer's disease and other neurodegenerative disorders. Behav Brain Funct 2006; 2: 15.
32. Reiter RJ. Oxidative damage in the central nervous system: Protection by melatonin. Prog Neurobiol 1998; 56: 359-84.
33. Muñoz-Hoyos A, Sánchez-Forte M. Molina-Carballo A, et al. Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998; 13: 501-9.
34. Reiter RJ, Cabrera J, Sainz RM, et al. Melatonin as a pharmacological agent against neuronal loss in experimental models of Huntington's disease, Alzheimer's disease and parkinsonism. Ann NY Acad Sci 1999; 890: 471-85.
35. Pappolla MA, Chyan YJ, Poeggeler B, et al. An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer's disease. J Neural Transm 2000; 107: 203-31.
36. Reiter RJ, Acuña-Castroviejo D, Tan D-X, et al. Free radicalmediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann NY Acad Sci 2001; 939: 200-15.
37. Cuzzocrea S, Reiter RJ. Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury. Eur J Pharmacol 2001; 426: 1-10.
38. Matsubara E, Bryant-Thomas T, Pacheco Quinto J, et al. Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. J Neurochem 2003; 85: 1101-8.
39. Beni SM, Kohen R, Reiter RJ, et al. Melatonin-induced neuroprotection after closed head injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-kappaB and AP-1. FASEB J 2004; 18: 149-51.
40. Hardeland R, Poeggeler B. Actions of melatonin, its structural and functional analogs in the central nervous system and the significance of metabolism. Cent Nerv Syst Agents Med Chem 2007; 7: 289-303.
41. Reiter RJ, Manchester LC, Tan D-X. Neurotoxins: free radical mechanisms and melatonin protection. Curr Neuropharmacol 2010; 8: 194-210.
42. Srinivasan V, Pandi-Perumal SR, Maestroni GJM, et al. Role of melatonin in neurodegenerative diseases. Neurotox Res 2005; 7: 293-318.
43. Rosales-Corral SA, Acuña-Castroviejo D, Coto-Montes A, et al. Alzheimer's disease: pathological mechanisms and the beneficial role of melatonin. J Pineal Res 2012; 52: 167-202.
44. Hardeland R, Cardinali DP, Brown GM, et al. Melatonin and brain inflammaging. Prog Neurobiol 2015; 127-128: 46-63.
45. 2 are decreased in Alzheimer's disease. Eur J Histochem 2006; 50: 311-6.
46. 1-receptor alterations in patients with Alzheimer's disease. Neurosci Lett 2001; 308: 9-12.
47. Wu YH, Swaab DF. Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease. Sleep Med 2007; 8: 623-36.
48. 1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer's disease. Neurobiol Aging 2007; 28: 1239-47.
49. 2 melatonin receptor expression in Alzheimer's disease. J Pineal Res 2005; 38: 10-6.
50. Bahna SG, Sathiyapalan A, Foster JA, et al. Regional upregulation of hippocampal melatonin MT2 receptors by valproic acid: therapeutic implications for Alzheimer's disease. Neurosci Lett 2014; 576: 84-7.
51. 2 melatonin receptor subtype is present in human retina and decreases in Alzheimer's disease. Curr Alzheimer Res 2007; 4: 47-51.
52. Caballero B, Vega-Naredo I, Sierra V, et al. Favorable effects of a prolonged treatment with melatonin on the level of oxidative damage and neurodegeneration in senescence-accelerated mice. J Pineal Res 2008; 45: 302-11.
53. Sánchez-Hidalgo M, Guerrero Montávez JM, Carrascosa-Salmoral M del P, et al. Decreased MT1 and MT2 melatonin receptor expression in extrapineal tissues of the rat during physiological aging. J Pineal Res 2009; 46: 29-35.
54. Hill SM, Cheng C, Yuan L, et al. Declining melatonin levels and MT1 receptor expression in aging rats is associated with enhanced mammary tumor growth and decreased sensitivity to melatonin. Breast Cancer Res Treat 2011; 127: 91-8.
55. Hill SM, Cheng C, Yuan L, et al. Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth. Curr Aging Sci 2013; 6: 125-33.
56. Singh AK, Haldar C. Age dependent nitro-oxidative load and melatonin receptor expression in the spleen and immunity of goat Capra hircus. Exp Gerontol 2014; 60: 72-8.
57. Hardeland R. Melatonin, noncoding RNAs, messenger RNA stability and epigenetics evidence, hints, gaps and perspectives. Int J Mol Sci 2014; 15: 18221-52.
58. 1 receptor, HDAC and MeCP2 mRNA expression in C6 glioma cells. Eur J Pharmacol 2008; 589: 45-48.
59. Esposito T, Magliocca S, Formicola D et al. piR-015520 belongs to Piwi-associated RNAs regulates expression of the human melatonin receptor 1A gene. PloS One 2011; 6: e22727.
60. Nakamura E, Kozaki K, Tsuda H, et al. Frequent silencing of a putative tumor suppressor gene melatonin receptor 1 A (MTNR1A) in oral squamous-cell carcinoma. Cancer Sci 2008; 99: 1390-400.
61. Godson C, Reppert SM. The Mel1a melatonin receptor is coupled to parallel signal transduction pathways. Endocrinology 1997; 138: 397-404.
62. Dubocovich ML, Rivera-Bermudez MA, Gerdin MJ, et al. Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front Biosci 2003; 8: d1093-108.
63. Hardeland R. Melatonin: Signaling mechanisms of a pleiotropic agent. BioFactors 2009; 35: 183-92.
64. Chaste P, Clement N, Mercati P, et al. Identification of pathwaybiased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population. PloS One 2010; 5: e11495.
65. Chaste P, Clement N, Goubran Botros H, et al. Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders. J Pineal Res 2011; 51: 394-9.
66. Ebisawa T. Circadian rhythms in the CNS and peripheral clock disorders: human sleep disorders and clock genes. J Pharmacol Sci 2007; 103: 150-4.
67. Okawa M, Uchiyama M. Circadian rhythm sleep disorders and entrainment pathology in delayed sleep phase and non-24-h sleepwake syndrome. Sleep Med Rev 2007; 11: 485-96.
68. Jones KH, Ellis J, von Schantz M, et al. Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities. J Sleep Res 2007; 18: 12-6.
69. Dijk DJ, Archer SN. PERIOD3, circadian phenotypes, and sleep homeostasis. Sleep Med Rev 2010; 14: 151-60.
70. Lázár AS, Slak A, Santhi N, et al. Sleep, diurnal preference, health, and psychological well-being: a prospective single-allelic-variation study. Chronobiol Int 2012; 29: 131-46.
71. Viola AU, Archer SN, James LM, et al. PER3 polymorphism predicts sleep structure and waking performance. Curr Biol 2007; 17: 613-8.
72. Viola AU, Chellappa SL, Archer SN, et al. Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of PER3 polymorphism. Neurobiol Aging 2012; 33: 1010. e17-27.
73. Karthikeyan R, Marimuthu G, Ramasubramanian C, et al. Association of Per3 length polymorphism with bipolar I disorder and schizophrenia. Neuropsychiatr Dis Treat 2014; 10: 2325-30.
74. Benedetti F, Dallaspezia S, Colombo C, et al. A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder. Neurosci Lett 2008; 445: 184-7.
75. Archer SN, Carpen JD, Gibson M, et al. Polymorphism in the PER3 promoter associates with diurnal preference and delayed sleep phase disorder. Sleep 2010; 33: 695-701.
76. Kovanen L, Kaunisto M, Donner K, et al. CRY2 genetic variants associate with dysthymia. PLoS One 2013; 8: e71450.
77. Etain B, Jamain S, Milhiet V, et al. Association between circadian genes, bipolar disorders and chronotypes. Chronobiol Int 2014; 31: 807-14.
78. Pawlak J, Dmitrzak-Weglarz M, Maciukiewicz M, et al. Suicidal behavior in the context of disrupted rhythmicity in bipolar disorder-data from an association study of suicide attempts with clock genes. Psychiatry Res 2015; 226: 517-20.
79. Kim HI, Lee HJ, Cho CH, et al. Association of CLOCK, ARNTL and NPAS2 gene polymorphisms and seasonal variations in mood and behavior. Chronobiol Int 2015; 32: 785-91.
80. Yang Z, Matsumoto A, Nakayama K, et al. Circadian-relevant genes are highly polymorphic in autism spectrum disorders patients. Brain Dev 2016; 38(1): 91-9.
81. Erren TC, Morfeld P, Stork J, et al. Shift work, chronodisruption and cancer? The IARC 2007 challenge for research and prevention and 10 theses from the Cologne Colloquium 2008. Scand J Work Environ Health 2009; 35: 74-9.
82. Erren TC, Reiter RJ. Defining chronodisruption. J Pineal Res 2009; 46: 245-7.
83. Reiter RJ, Tan DX, Korkmaz A, et al. Light at night, chronodisruption, melatonin suppression, and cancer risk: a review. Crit Rev Oncog 2007; 13: 303-28.
84. Bonmati-Carrion MA, Arguelles-Prieto R, Martinez-Madrid MJ, et al. Protecting the melatonin rhythm through circadian healthy light exposure. Int J Mol Sci 2014; 15: 23448-500.
85. Hofman MA. The human circadian clock and aging. Chronobiol Int 2000; 17: 245-59.
86. Hofman MA, Swaab DF. Living by the clock: The circadian pacemaker in older people. Ageing Res Rev 2006; 5: 33-51.
87. Challet E, Dumont S, Mehdi MK, et al. Aging-like circadian disturbances in folate-deficient mice. Neurobiol Aging 2013; 34: 1589-98.
88. Silver R, Schwartz WJ. The suprachiasmatic nucleus is a functionally heterogeneous timekeeping organ. Methods Enzymol 2005; 393: 451-65.
89. Belle MD, Diekman CO, Forger DB, et al. Daily electrical silencing in the mammalian circadian clock. Science 2009; 326: 281-4.
90. Pandi-Perumal SR, Srinivasan V, Maestroni GJM, et al. Melatonin-Nature's most versatile biological signal? FEBS J 2006; 273: 2813-38.
91. Hardeland R. Melatonin metabolism in the central nervous system. Curr Neuropharmacol 2010; 8: 168-81.
92. 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.
93. Hardeland R, Ressmeyer A-R, Zelosko V, et al. Metabolites of melatonin: Formation and properties of the methoxylated kynuramines AFMK and AMK. In: Haldar C, Singh SS, Eds. Recent Advances in Endocrinology and Reproduction: Evolutionary, Biotechnological and Clinical Applications. Varanasi: Banaras Hindu University 2004; pp. 21-38.
94. Hardeland R, Tan D-X, Reiter RJ. Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines. J Pineal Res 2009; 47: 109-26.
95. Tan D-X, Hardeland R, Manchester LC, et al. Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical. J Pineal Res 2003; 34: 249-59.
96. Rosen J, Than NN, Koch D, et al. Interactions of melatonin and its metabolites with the ABTS cation radical: extension of the radical scavenger cascade and formation of a novel class of oxidation products, C2-substituted 3-indolinones. J Pineal Res 2006; 41: 374-81.
97. 1-acetyl-5-methoxykynuramine) with reactive nitrogen species: Formation of novel compounds, 3-acetamidomethyl-6-methoxycinnolinone and 3-nitro-AMK. J Pineal Res 2005; 39: 251-60.
98. 1-acetyl-5-methoxykynuramine (AMK) with the tyrosine side-chain fragment, 4-ethylphenol. Redox Rep 2008; 13: 102-8.
99. 1-acetyl-5-methoxykynuramine. J Pineal Res 2007; 43: 382-8.
100. Hardeland R. Melatonin and its metabolites as anti-nitrosating and anti-nitrating agents. J Exp Integ Med 2011; 1: 67-81.
101. Hirata F, Hayaishi O, Tokuyama T, et al. In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem 1974; 249: 1311-3.
102. 2-formyl-5-methoxykynuramine, in cerebrospinal fluid of patients with meningitis: a possible immunomodulatory mechanism. J Pineal Res 2005; 39: 302-6.
103. 2A/2C receptors: mutual improvement of sleep, cognition and mood? Eur J Neurosci 2009; 29: 1795-809.
104. Mulchahey JJ, Goldwater DR, Zemlan FP. 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: 1843-56.
105. Poeggeler B, Thuermann S, Dose A, et al. Melatonin's unique radical scavenging properties-Roles of its functional substituents as revealed by a comparison with its structural analogs. J Pineal Res 2002; 33: 20-30.
106. Laudon M, Peleg-Shulman T. Novel pyrone-indole derivatives and process for their preparation. United States Patent US20080027121A1; 2008.
107. He P, Ouyang X, Zhou S, et al. A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease. Horm Behav 2013; 64: 1-7.
108. Chen C, Fichna J, Laudon M, et al. Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain. World J Gastroenterol 2014; 20: 1298-1304.
109. Oertel R, Goltz L, Kirch W. Elucidation of Neu-P11 metabolism in urine of volunteers by liquid chromatography-tandem mass spectrometry. J Chromatrogr A 2013; 1278: 69-75.
110. Drijfhout WJ, de Vries JB, Homan EJ, et al. Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude. Eur J Pharmacol 1999; 382: 157-66.
111. Hardeland R, Fuhrberg B, Lax P. Aryl acylamidase of the dinoflagellate Gonyaulax polyedra. In: Hardeland R, Ed. Metabolism and Cellular Dynamics of Indoles. Göttingen: University of Göttingen 1996, pp. 47-51.
112. Bourin M, Mocaër E, Porsolt R. Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: in volvement of melatonin and serotonin receptors. J Psychiatry Neurosci 2004; 29: 126-33.
113. 2C receptors in Wistar rats. Psychopharmacology (Berl) 2003; 170: 17-22.
114. Bogaards JJP, Hissink EM, Briggs M, et al. Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling. Eur J Pharm Sci 2000; 12: 117-24.
115. Hardeland R. Agomelatine and the risk of hepatotoxicity. J Symptoms Signs 2014; 3: 341-6.
116. 2 receptor agonist. Neuropharmacology 2005; 48: 301-10.
117. 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: 140-8.
118. Catt JD, Johnson G, Keavy DJ, et al. Benzodioxole, benzofuran, dihydrobenzofuran, and benzodioxane melatonergic agents. World Patent WO-09825606; 1998.
119. Rajaratnam SMW, Polymeropoulos MH, Fisher DM, et al. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: Two randomised controlled multicentre trials. Lancet 2009; 373: 482-91.
120. Cardinali D, Golombek D. Let there be sleep-on time. Lancet 2009; 373: 439-41.
121. Hardeland R. Tasimelteon, a melatonin agonist for the treatment of insomnia and circadian rhythm sleep disorders. Curr Opin Investig Drugs 2009; 10: 691-701.
122. Rivara S, Pala D, Lodola A, et al. MT1-selective melatonin receptor ligands: synthesis, pharmacological evaluation, and molecular dynamics investigation of N-{[(3-O-substituted)anilino]alkyl} amides. ChemMedChem 2012; 7: 1954-64.
123. Pala D, Beuming T, Sherman W, et al. Structure-based virtual screening of MT2 melatonin receptor: influence of template choice and structural refinement. J Chem Inf Model 2013; 53: 821-35.
124. Pala D, Scalvini L, Lodola A, et al. Synthesis and characterization of new bivalent agents as melatonin-and histamine H3-ligands. Int J Mol Sci 2014; 15: 16114-33.
125. de la Fuente Revenga M, Fernández-Sáez N, Herrera-Arozamena C, et al. Novel N-acetyl bioisosteres of melatonin: melatonergic receptor pharmacology, physicochemical studies, and phenotypic assessment of their neurogenic potential. J Med Chem 2015; 58: 4998-5014.
126. Rivara S, Lodola A, Mor M, et al. N-(substituted-anilinoethyl) amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands. J Med Chem 2007; 50: 6618-26.
127. Rivara S, Mor M, Bedini A, et al. Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem 2008; 8: 954-68.
128. Rivara S, Vacondio F, Fioni A, et al. N-(Anilinoethyl)amides: design and synthesis of metabolically stable, selective melatonin receptor ligands. ChemMedChem 2009; 4: 1746-55.
129. Lewy AJ, Ahmed S, Jackson JM, and Sack, et al. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int 1992; 9: 380-92.
130. Burgess HJ, Revell VL, Eastman CI. A three pulse phase response curve to three milligrams of melatonin in humans. J Physiol 2008; 586: 639-47.
131. Keijzer H, Smits MG, Duffy JF, et al. Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders. Sleep Med Rev 2014; 18: 333-9.
132. 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: 915-36.
133. Zemlan FP, Mulchahey JJ, Scharf MB, 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: 384-90.
134. 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.
135. Roth T, Seiden D, Sainati S, et al. Effects of ramelteon on patientreported sleep latency in older adults with chronic insomnia. Sleep Med 2006; 7: 312-8.
136. Hardeland R, Poeggeler B, Srinivasan V, et al. Melatonergic drugs in clinical practice. Arzneimittelforschung 2008; 58: 1-10.
137. Mayer G, Wang-Weigand S, Roth-Schechter B, et al. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep 2009; 32: 351-60.
138. Richardson GS, Zammit G, Wang-Weigand S, et al. Safety and subjective sleep effects of ramelteon administration in adults and older adults with chronic primary insomnia: a 1-year, open-label study. J Clin Psychiatry 2009; 70: 467-76.
139. Pandi-Perumal SR, Srinivasan V, Spence DW, et al. Ramelteon: A review of its therapeutic potential in sleep disorders. Adv Ther 2009; 26: 613-26.
140. Srinivasan V, Pandi-Perumal SR, Trahkt I, et al. Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci 2009; 119: 821-46.
141. Pandi-Perumal SR, Spence DW, Verster JC, et al. Pharmacotherapy of insomnia with ramelteon: Safety, efficacy and clinical applications. J Cent Nerv Syst Dis 2011; 3: 51-65.
142. Nduhirabandi F, du Toit EF, Lochner A. Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities? Acta Physiol (Oxf) 2012; 205: 209-23.
143. Srinivasan V, Ohta Y, Espino J, et al. Metabolic syndrome, its pathophysiology and the role of melatonin. Recent Pat Endocr Metab Immune Drug Discov 2013; 7: 11-25.
144. Vinogradova I, Anisimov V. Melatonin prevents the development of the metabolic syndrome in male rats exposed to different light/dark regimens. Biogerontology 2013; 14: 401-9.
145. Navarro-Alarcón M, Ruiz-Ojeda FJ, Blanca-Herrera RM, et al. Melatonin and metabolic regulation: a review. Food Funct 2014; 5: 2806-32.
146. Corbalán-Tutau MD, Gómez-Abellán P, Madrid JA, et al. Toward a chronobiological characterization of obesity and metabolic syndrome in clinical practice. Clin Nutr 2015; 34: 477-83.
147. Clark IA, Vissel B. Treatment implications of the altered cytokineinsulin axis in neurodegenerative disease. Biochem Pharmacol 2013; 8: 862-871.
148. De Felice FG, Lourenco MV, Ferreira ST. How does brain insulin resistance develop in Alzheimer's disease? Alzheimers Dement 2014: 10 (Suppl 1): S26-32.
149. de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol 2014; 88: 548-59.
150. Wang PP, She MH, He PP, et al. Piromelatine decreases triglyceride accumulation in insulin-resistant 3T3-L1 adipocytes: role of ATGL and HSL. Biochimie 2013; 95: 1650-4.
151. Li X, Cai S, Yin W, et al. Neu-P11 reduces clock/apelin expression in insulin-resistant mouse adipocyte model. Acta Biochim Biophys Sin (Shanghai) 2013; 45: 798-900.
152. Huang L, Zhang C, Hou Y, et al. Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats. Eur Rev Med Pharmacol Sci 2013; 17: 2449-56.
153. She M, Hu X, Zhang C, et al. Piromelatine, a novel melatonin receptor agonist, stabilizes metabolic profiles and amleriorates insulin resistance inchronic sleep restricted rats. Eur J Pharmacol 2014; 727: 60-5.
154. Manchester LC, Coto-Montes A, Boga JA, et al. Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res 2015; 59(4): 403-19.
155. Tuli HS, Kashyap D, Sharma AK and Sandhu SS. Molecular aspects of melatonin (MLT)-mediated therapeutic effects. Life Sci 2015; 135: 147-157.
156. 2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003; 306: 954-64.
157. 2C receptors. World J Biol Psychiatry 2011; 12: 574-87.
158. Pandi-Perumal SR, Srinivasan V, Cardinali DP and Monti MJ. Could agomelatine be the ideal antidepressant? Expert Rev Neurother 2006; 6: 1595-608.
159. Srinivasan V, Brzezinski A, Pandi-Perumal SR, et al. Melatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics? Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 913-23.
160. Cardinali DP, Srinivasan V, Brzezinski A, et al. Melatonin and its analogs in insomnia and depression. J Pineal Res 2012; 52: 365-75.
161. Howland RH. Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults. Neuropsychiatr Dis Treat 2009; 5: 563-76.
162. Anonymous. Agomelatine: new drug. Adverse effects and no proven efficacy. Prescrire Int 2009; 18: 241-5.
163. Howland RH. A benefit-risk assessment of agomelatine in the treatment of major depression. Drug Saf 2011; 34: 709-31.
164. Guaiana G, Gupta S, Chiodo D, et al. Agomelatine versus other antidepressive agents for major depression. Cochrane Database Syst Rev 2013; 12: CD008851.
165. Howland RH. Publication bias and outcome reporting bias: agomelatine as a case example. J Psychosoc Nurs Ment Health Serv 2011; 49: 11-4.
166. Voican CS, Corruble E, Naveau S, et al. Antidepressant-induced liver injury: A review for clinicians. Am J Psychiatry 2014; 171: 404-15.
167. Cohen-Mansfield J, Garfinkel D, Lipson S. Melatonin for treatment of sundowning in elderly patients with dementia-a preliminary study. Arch Gerontol Geriatr 2000; 31: 65-76.
168. Mahlberg R, Kunz D, Sutej I, et al. Melatonin treatment of daynight rhythm disturbances and sundowning in Alzheimer's disease: an open-label pilot study using actigraphy. J Clin Psychopharmacol 2004; 24: 456-9.
169. Brusco LI, Marquez M, Cardinali DP. Melatonin treatment stabilizes chronobiologic and cognitive symptoms in Alzheimer's disease. Neuroendocrinol Lett 2000; 21: 39-42.
170. Cardinali DP, Brusco LI, Liberczuk C, et al. The use of melatonin in Alzheimer's disease. Neuroendocrinol Lett 2002; 23 (Suppl 1): 20-3.
171. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, et al. Melatonin: buffering the immune system. Int J Mol Sci 2013; 14: 8638-83.
172. Cardinali DP, García AP, Cano P, et al. Melatonin role in experimental arthritis. Curr Drug Targets Immune Endocr Metabol Disord 2004; 4: 1-10.
173. Maestroni GJ, Cardinali DP, Esquifino AI, et al. Does melatonin play a disease-promoting role in rheumatoid arthritis? J Neuroimmunol 2005; 158: 106-11.
174. Srinivasan V, Cardinali DP, Srinivasan US, et al. Therapeutic potential of melatonin and its analogs in Parkinson's disease: focus on sleep and neuroprotection. Ther Adv Neurol Disord 2011; 4: 297-317.
175. Willis GL. Parkinson's disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process. Rev Neurosci 2008; 19: 245-316.
176. Willis GL. The role of ML-23 and other melatonin analogues in the treatment and management of Parkinson's disease. Drug News Perspect 2005; 18: 437-44.