Agomelatine: Mechanism of action and pharmacological profile in relation to antidepressant properties

British Journal of Pharmacology

Volumn 171, Issue 15, 2014, Pages 3604-3619

  Guardiola Lemaitre, B ^a   De Bodinat, C ^b   Delagrange, P ^c   Millan, M J ^c   Munoz, C ^d   Mocaer E ^b  

^a Scientific Direction Research and Development   (France)

^b IRIS Institut de Recherches Internationales Servier   (France)

^c INSTITUT DE RECHERCHES SERVIER   (France)

^d INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

Author keywords

agomelatine; antidepressant; melatonin receptors

Indexed keywords

AGOMELATINE; BRAIN DERIVED NEUROTROPHIC FACTOR; CLORAZEPATE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; DOUBLECORTIN; GLUTAMIC ACID; GLYCOGEN SYNTHASE KINASE 3; INTERLEUKIN 1BETA; INTERLEUKIN 6; MELATONIN 1 RECEPTOR; MELATONIN 2 RECEPTOR; MICROTUBULE ASSOCIATED PROTEIN 2; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PER1 PROTEIN; PER2 PROTEIN; SEROTONIN 2C RECEPTOR; TRANSCRIPTION FACTOR CLOCK; VESICULAR GLUTAMATE TRANSPORTER; ACETAMIDE DERIVATIVE; ANTIDEPRESSANT AGENT; ANXIOLYTIC AGENT; SEROTONIN 2 ANTAGONIST;

ANTIDEPRESSANT ACTIVITY; CHRONIC DRUG ADMINISTRATION; CHRONOBIOLOGY; CIRCADIAN RHYTHM; COGNITION; DEPRESSION; DOSAGE SCHEDULE COMPARISON; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MECHANISM; DRUG RECEPTOR BINDING; EVENING DOSAGE; FORCED SWIM TEST; GASTROINTESTINAL DISEASE; HIPPOCAMPUS; HUMAN; LIGHT DARK CYCLE; LONG TERM POTENTIATION; MEMORY CONSOLIDATION; MENTAL STRESS; MORNING DOSAGE; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; REM SLEEP; REVIEW; SEXUAL DYSFUNCTION; SLEEP DISORDER; SLOW WAVE SLEEP; SUPRACHIASMATIC NUCLEUS; TAIL SUSPENSION TEST; TRANQUILIZING ACTIVITY; VOGEL TEST; WITHDRAWAL SYNDROME; AGONISTS; ANIMAL; ANXIETY; METABOLISM;

ACETAMIDES; ANIMALS; ANTI-ANXIETY AGENTS; ANTIDEPRESSIVE AGENTS; ANXIETY; CIRCADIAN RHYTHM; DEPRESSION; HUMANS; NEUROGENESIS; RECEPTOR, MELATONIN, MT1; RECEPTOR, MELATONIN, MT2; SEROTONIN 5-HT2 RECEPTOR ANTAGONISTS;

EID: 84904556775     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12720     Document Type: Review

References (157)

1. Adam G, Guardiola-Lemaitre B, Yous S, Lesieur D, Morgan P, Howell HE, etal. (1992). [New naphthalenic ligands of melatoninergic receptors]. J Pharm Belg 47: 374-380.
2. Aira Z, Buesa I, Salgueiro M, Bilbao J, Aguilera L, Zimmermann M, etal. (2010). Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury. Neuroscience 168: 831-841.
3. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA, Harmar AJ, and CGTP Collaborators (2013a). The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors. Br J Pharmacol 170: 1459-1581.
4. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA, Harmar AJ, and CGTP Collaborators (2013b). The Concise Guide to PHARMACOLOGY 2013/14: Transporters. Br J Pharmacol 170: 1706-1796.
5. Almeida RC, Souza DG, Soletti RC, Lopez MG, Rodrigues AL, Gabilan NH, (2006). Involvement of PKA, MAPK/ERK and CaMKII, but not PKC in the acute antidepressant-like effect of memantine in mice. Neurosci Lett 395: 93-97.
6. Aloyo VJ, Berg KA, Spampinato U, Clarke WP, Harvey JA, (2009). Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors. Pharmacol Ther 121: 160-173.
7. Armstrong SM, McNulty OM, Guardiola-Lemaitre B, Redman JR, (1993). Successful use of S20098 and melatonin in an animal model of delayed sleep-phase syndrome (DSPS). Pharmacol Biochem Behav 46: 45-49.
8. Audinot V, Mailliet F, Lahaye BC, Bonnaud A, Le Gall A, Amosse C, etal. (2003). New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol 16: 553-561.
9. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, etal. (2011). NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475: 91-95.
10. Banasr M, Duman RS, (2007). Regulation of neurogenesis and gliogenesis by stress and antidepressant treatment. CNS Neurol Disord Drug Targets 6: 311-320.
11. Banasr M, Soumier A, Hery M, Mocaer E, Daszuta A, (2006). Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry 59: 1087-1096.
12. Barden N, Shink E, Labbe M, Vacher R, Rochford J, Mocaer E, (2005). Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. Prog Neuropsychopharmacol Biol Psychiatry 29: 908-916.
13. Baune BT, Miller R, McAfoose J, Johnson M, Quirk F, Mitchell D, (2010). The role of cognitive impairment in general functioning in major depression. Psychiatry Res 176: 183-189.
14. Bertaina-Anglade V, la Rochelle CD, Boyer PA, Mocaer E, (2006). Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model. Behav Pharmacol 17: 703-713.
15. Bertaina-Anglade V, Drieu-La-Rochelle C, Mocaer E, Seguin L, (2011). Memory facilitating effects of agomelatine in the novel object recognition memory paradigm in the rat. Pharmacol Biochem Behav 98: 511-517.
16. Bessa JM, Ferreira D, Melo I, Marques F, Cerqueira JJ, Palha JA, etal. (2009). The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol Psychiatry 14: 764-773, 739.
17. de Bodinat C, Guardiola-Lemaitre B, Mocaer E, Renard P, Munoz C, Millan MJ, (2010). Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov 9: 628-642.
18. Bonanno G, Giambelli R, Raiteri L, Tiraboschi E, Zappettini S, Musazzi L, etal. (2005). Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus. J Neurosci 25: 3270-3279.
19. Bonnefond C, Martinet L, Lesieur D, Adam G, Guardiola-Lemaitre B, (1993). Characterization of S-20098, a new melatonin analog. In:, Touitou Y, Arendt J, Pevet P, (eds). Melatonin and the Pineal Gland. From Basic Science to Clinical Application. Elsevier: Amsterdam, pp. 123-126.
20. Bourin M, Mocaer E, Porsolt R, (2004). Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci 29: 126-133.
21. Brea J, Castro-Palomino J, Yeste S, Cubero E, Parraga A, Dominguez E, etal. (2010). Emerging opportunities and concerns for drug discovery at serotonin 5-HT2B receptors. Curr Top Med Chem 10: 493-503.
22. Bunney JN, Potkin SG, (2008). Circadian abnormalities, molecular clock genes and chronobiological treatments in depression. Br Med Bull 86: 23-32.
23. Cajochen C, Krauchi K, Mori D, Graw P, Wirz-Justice A, (1997). Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis. Am J Physiol 272: R1189-R1196.
24. Calabrese F, Molteni R, Gabriel C, Mocaer E, Racagni G, Riva MA, (2011). Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine. Psychopharmacology (Berl) 215: 267-275.
25. Castanho A, Bothorel B, Seguin L, Mocaer E, Pevet P, (2014). Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of two clock outputs: melatonin and temperature rhythms. Chronobiol Int 31: 371-381.
26. Cervantes-Duran C, Vidal-Cantu GC, Barragan-Iglesias P, Pineda-Farias JB, Bravo-Hernandez M, Murbartian J, etal. (2012). Role of peripheral and spinal 5-HT2B receptors in formalin-induced nociception. Pharmacol Biochem Behav 102: 30-35.
27. Chagraoui A, Protais P, Filloux T, Mocaer E, (2003). Agomelatine(S 20098) antagonizes the penile erections induced by the stimulation of 5-HT2C receptors in Wistar rats. Psychopharmacology (Berl) 170: 17-22.
28. Chanrion B, Mannoury LC, Gavarini S, Seimandi M, Vincent L, Pujol JF, etal. (2008). Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulation of cell surface expression and signal transduction. Mol Pharmacol 73: 748-757.
29. Chenu F, El MM, Blier P, (2013). Electrophysiological effects of repeated administration of agomelatine on the dopamine, norepinephrine, and serotonin systems in the rat brain. Neuropsychopharmacology 38: 275-284.
30. Cirulli F, Alleva E, (2009). The NGF saga: from animal models of psychosocial stress to stress-related psychopathology. Front Neuroendocrinol 30: 379-395.
31. Conboy L, Tanrikut C, Zoladz PR, Campbell AM, Park CR, Gabriel C, etal. (2009). The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats. Int J Neuropsychopharmacol 12: 329-341.
32. Craig LA, McDonald RJ, (2008). Chronic disruption of circadian rhythms impairs hippocampal memory in the rat. Brain Res Bull 76: 141-151.
33. Dagyte G, Trentani A, Postema F, Luiten PG, Den Boer JA, Gabriel C, etal. (2010). The novel antidepressant agomelatine normalizes hippocampal neuronal activity and promotes neurogenesis in chronically stressed rats. CNS Neurosci Ther 16: 195-207.
34. Dagyte G, Crescente I, Postema F, Seguin L, Gabriel C, Mocaer E, etal. (2011). Agomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress. Behav Brain Res 218: 121-128.
35. David DJ, Gabriel-Gracia C, Mocaer E, Tanaka K, Gardier AM, Hen R, (2008). [Hippocampal neurogenesis may be required for behavioral effects of Agomelatine in the novelty suppressed feeding test e]. Program No. 160.10/EE23 2008 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2008. Online.
36. David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, etal. (2009). Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62: 479-493.
37. Dekeyne A, Mannoury LC, Gobert A, Brocco M, Lejeune F, Serres F, etal. (2008). S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models. Psychopharmacology (Berl) 199: 549-568.
38. Delagrange P, Guardiola-Lemaitre B, (1997). Melatonin, its receptors, and relationships with biological rhythm disorders. Clin Neuropharmacol 20: 482-510.
39. Descamps A, Rousset C, Millan MJ, Spedding M, Delagrange P, Cespuglio R, (2009). Influence of the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist, agomelatine, on the rat sleep-wake cycle architecture. Psychopharmacology (Berl) 205: 93-106.
40. Devan BD, Goad EH, Petri HL, Antoniadis EA, Hong NS, Ko CH, etal. (2001). Circadian phase-shifted rats show normal acquisition but impaired long-term retention of place information in the water task. Neurobiol Learn Mem 75: 51-62.
41. Diaz-Mataix L, Mocaer E, Seguin L, LeDoux JE, (2012). The antidepressant agomelatine reduces fear long term memory but not acquisition or short term expression of fear memories. Involvement of the melatonergic agonist and 5HT2C antagonist properties. Eur Neuropsychopharmacol 22: S270.
42. Dubocovich ML, (2006). Agomelatine targets a range of major depressive disorder symptoms. Curr Opin Investig Drugs 7: 670-680.
43. Dubocovich ML, Hudson RL, Sumaya IC, Masana MI, Manna E, (2005). Effect of MT1 melatonin receptor deletion on melatonin-mediated phase shift of circadian rhythms in the C57BL/6 mouse. J Pineal Res 39: 113-120.
44. El Yacoubi M, Bouali S, Popa D, Naudon L, Leroux-Nicollet I, Hamon M, etal. (2003). Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci U S A 100: 6227-6232.
45. El Yacoubi M, Dubois M, Gabriel C, Mocaer E, Vaugeois JM, (2011). Chronic agomelatine and fluoxetine induce antidepressant-like effects in H/Rouen mice, a genetic mouse model of depression. Pharmacol Biochem Behav 100: 284-288.
46. Fekete M, van Ree JM, Niesink RJ, de Wied D, (1985). Disrupting circadian rhythms in rats induces retrograde amnesia. Physiol Behav 34: 883-887.
47. Fuchs E, (2005). Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder. CNS Spectr 10: 182-190.
48. Galeotti N, Ghelardini C, (2012). Regionally selective activation and differential regulation of ERK, JNK and p38 MAP kinase signalling pathway by protein kinase C in mood modulation. Int J Neuropsychopharmacol 15: 781-793.
49. Germain A, Kupfer DJ, (2008). Circadian rhythm disturbances in depression. Hum Psychopharmacol 23: 571-585.
50. Gourley SL, Wu FJ, Kiraly DD, Ploski JE, Kedves AT, Duman RS, etal. (2008). Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression. Biol Psychiatry 63: 353-359.
51. Grassi-Zucconi G, Semprevivo M, Mocaer E, Kristensson K, Bentivoglio M, (1996). Melatonin and its new agonist S-20098 restore synchronized sleep fragmented by experimental trypanosome infection in the rat. Brain Res Bull 39: 63-68.
52. Guardiola-Lemaitre B, Quera-Salva MA, (2011). Melatonin and regulation of sleep and circadian disorders. In:, Krygeer MH, Roth T, Dement WC, (eds). Principles and Practice of Sleep medicine, Elsevier edn. Elsevier-Saunders: Philadelphia, pp. 420-430.
53. Hammar A, Sorensen L, Ardal G, Oedegaard KJ, Kroken R, Roness A, etal. (2010). Enduring cognitive dysfunction in unipolar major depression: a test-retest study using the Stroop paradigm. Scand J Psychol 51: 304-308.
54. Hanoun N, Mocaer E, Boyer PA, Hamon M, Lanfumey L, (2004). Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain. Neuropharmacology 47: 515-526.
55. Hashimoto K, (2011). The role of glutamate on the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 35: 1558-1568.
56. Heisler LK, Zhou L, Bajwa P, Hsu J, Tecott LH, (2007). Serotonin 5-HT(2C) receptors regulate anxiety-like behavior. Genes Brain Behav 6: 491-496.
57. Hickie IB, Rogers NL, (2011). Novel melatonin-based therapies: potential advances in the treatment of major depression. Lancet 378: 621-631.
58. Hoshaw BA, Malberg JE, Lucki I, (2005). Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects. Brain Res 1037: 204-208.
59. Iwata M, Shirayama Y, Ishida H, Kawahara R, (2006). Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats. Neuroscience 141: 1301-1313.
60. Jaffre F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, etal. (2004). Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation: control of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts. Circulation 110: 969-974.
61. Jope RS, Roh MS, (2006). Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets 7: 1421-1434.
62. Kamal M, Guillaume JL, Daulat A, Chen P, Mannoury la Cour C, Millan M, etal. (2010). Evidence for functional heteromerization of melatonin MT1 and MT2 receptors with serotonin (5-HT)2C receptors. Int J Neuropsychopharmacol 13: P3-P23.
63. van de Kar LD, Lorens SA, (1979). Differential serotonergic innervation of individual hypothalamic nuclei and other forebrain regions by the dorsal and median midbrain raphe nuclei. Brain Res 162: 45-54.
64. Kasper S, Hajak G, Wulff K, Hoogendijk WJ, Montejo AL, Smeraldi E, etal. (2010). Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline. J Clin Psychiatry 71: 109-120.
65. Kennaway DJ, Moyer RW, (1998). Serotonin 5-HT2c agonists mimic the effect of light pulses on circadian rhythms. Brain Res 806: 257-270.
66. Kennaway DJ, Moyer RW, Voultsios A, Varcoe TJ, (2001). Serotonin, excitatory amino acids and the photic control of melatonin rhythms and SCN c-FOS in the rat. Brain Res 897: 36-43.
67. Kennedy SH, Rizvi SJ, (2010). Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs 24: 479-499.
68. Kennedy SH, Rizvi S, Fulton K, Rasmussen J, (2008). A double-blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR. J Clin Psychopharmacol 28: 329-333.
69. Koresh O, Kozlovsky N, Kaplan Z, Zohar J, Matar MA, Cohen H, (2012). The long-term abnormalities in circadian expression of Period 1 and Period 2 genes in response to stress is normalized by agomelatine administered immediately after exposure. Eur Neuropsychopharmacol 22: 205-221.
70. Krauchi K, Cajochen C, Mori D, Graw P, Wirz-Justice A, (1997). Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature. Am J Physiol 272: R1178-R1188.
71. Kronfeld-Schor N, Einat H, (2012). Circadian rhythms and depression: human psychopathology and animal models. Neuropharmacology 62: 101-114.
72. Ladurelle N, Gabriel C, Viggiano A, Mocaer E, Baulieu EE, (2012). Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC. Psychopharmacology (Berl) 221: 493-509.
73. Lee SH, Chun W, Kong PJ, Han JA, Cho BP, Kwon OY, etal. (2006). Sustained activation of Akt by melatonin contributes to the protection against kainic acid-induced neuronal death in hippocampus. J Pineal Res 40: 79-85.
74. Leproult R, Van Onderbergen A, L'hermite-Baleriaux M, Van Cauter E, Copinschi G, (2005). 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: 298-304.
75. Li JZ, Bunney BG, Meng F, Hagenauer MH, Walsh DM, Vawter MP, etal. (2013). Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc Natl Acad Sci U S A 110: 9950-9955.
76. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, etal. (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329: 959-964.
77. Li X, Jope RS, (2010). Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology 35: 2143-2154.
78. Lin SY, Chang WJ, Lin CS, Huang CY, Wang HF, Sun WH, (2011). Serotonin receptor 5-HT2B mediates serotonin-induced mechanical hyperalgesia. J Neurosci 31: 1410-1418.
79. 2C receptors in vivo: a phMRI challenge study in rats. Eur Neuropsychopharmacol 19: S259.
80. Machado-Vieira R, Salvadore G, Diazgranados N, Zarate CA Jr, (2009). Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther 123: 143-150.
81. Mairesse J, Silletti V, Laloux C, Zuena AR, Giovine A, Consolazione M, etal. (2013). Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats. Int J Neuropsychopharmacol 16: 323-338.
82. Marazziti D, Consoli G, Picchetti M, Carlini M, Faravelli L, (2010). Cognitive impairment in major depression. Eur J Pharmacol 626: 83-86.
83. Marrocco J, Reynaert ML, Gatta E, Gabriel C, Mocaer E, Di PS, etal. (2014). The effects of antidepressant treatment in prenatally stressed rats support the glutamatergic hypothesis of stress-related disorders. J Neurosci 34: 2015-2024.
84. Martinet L, Guardiola-Lemaitre B, Mocaer E, (1996). Entrainment of circadian rhythms by S-20098, a melatonin agonist, is dose and plasma concentration dependent. Pharmacol Biochem Behav 54: 713-718.
85. Martinotti G, Sepede G, Gambi F, Di IG, De BD, Di NM, etal. (2012). Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study. J Clin Psychopharmacol 32: 487-491.
86. McClung CA, (2007). Circadian genes, rhythms and the biology of mood disorders. Pharmacol Ther 114: 222-232.
87. Mendlewicz J, (2009). Disruption of the circadian timing systems: molecular mechanisms in mood disorders. CNS Drugs 23 (Suppl. 2): 15-26.
88. Milanese M, Tardito D, Musazzi L, Treccani G, Mallei A, Bonifacino T, etal. (2013). Chronic treatment with agomelatine or venlafaxine reduces depolarization-evoked glutamate release from hippocampal synaptosomes. BMC Neurosci 14: 75.
89. Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, etal. (2003). The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 306: 954-964.
90. Millan MJ, Brocco M, Gobert A, Dekeyne A, (2005). Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl) 177: 448-458.
91. Millan MJ, Marin P, Kamal M, Jockers R, Chanrion B, Labasque M, etal. (2011a). The melatonergic agonist and clinically active antidepressant, agomelatine, is a neutral antagonist at 5-HT(2C) receptors. Int J Neuropsychopharmacol 14: 768-783.
92. Millan MJ, Marin P, Kamal M, Jockers R, Chanrion B, Labasque M, etal. (2011b). The melatonergic agonist and clinically active antidepressant, agomelatine, is a neutral antagonist at 5-HT2C receptors. Int J Neuropsychopharmacol 14: 768-783.
93. Mitchell ND, Baker GB, (2010). An update on the role of glutamate in the pathophysiology of depression. Acta Psychiatr Scand 122: 192-210.
94. Miyamoto S, Asakura M, Sasuga Y, Osada K, Bodaiji N, Imafuku J, etal. (1997). Effects of long-term treatment with desipramine on microtubule proteins in rat cerebral cortex. Eur J Pharmacol 333: 279-287.
95. Molteni R, Calabrese F, Pisoni S, Gabriel C, Mocaer E, Racagni G, etal. (2010). Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration. World J Biol Psychiatry 11: 148-153.
96. Molteni R, Macchi F, Zecchillo C, Dell'agli M, Colombo E, Calabrese F, etal. (2013). Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine. Eur Neuropsychopharmacol 23: 1645-1655.
97. Monassier L, Laplante MA, Jaffre F, Bousquet P, Maroteaux L, de Champlain CJ, (2008). Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice. Hypertension 52: 301-307.
98. Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I, (2004). Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study. Int Clin Psychopharmacol 19: 271-280.
99. Morin LP, (1999). Serotonin and the regulation of mammalian circadian rhythmicity. Ann Med 31: 12-33.
100. Morley-Fletcher S, Mairesse J, Soumier A, Banasr M, Fagioli F, Gabriel C, etal. (2011). Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats. Psychopharmacology (Berl) 217: 301-313.
101. Moutsimilli L, Farley S, Dumas S, El Mestikawy S, Giros B, Tzavara ET, (2005). Selective cortical VGLUT1 increase as a marker for antidepressant activity. Neuropharmacology 49: 890-900.
102. Moyer RW, Kennaway DJ, (1999). Immunohistochemical localization of serotonin receptors in the rat suprachiasmatic nucleus. Neurosci Lett 271: 147-150.
103. Mukherjee S, Coque L, Cao JL, Kumar J, Chakravarty S, Asaithamby A, etal. (2010). Knockdown of CLOCK in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biol Psychiatry 68: 503-511.
104. Musazzi L, Mallei A, Tardito D, Gruber SH, El KA, Racagni G, etal. (2010a). Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression. J Psychiatr Res 44: 511-520.
105. Musazzi L, Milanese M, Farisello P, Zappettini S, Tardito D, Barbiero VS, etal. (2010b). Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants. PLoS ONE 5: e8566.
106. Navailles S, Moison D, Ryczko D, Spampinato U, (2006). Region-dependent regulation of mesoaccumbens dopamine neurons in vivo by the constitutive activity of central serotonin2C receptors. J Neurochem 99: 1311-1319.
107. Norman TR, Cranston I, Irons JA, Gabriel C, Dekeyne A, Millan MJ, etal. (2012). Agomelatine suppresses locomotor hyperactivity in olfactory bulbectomised rats: a comparison to melatonin and to the 5-HT(2c) antagonist, S32006. Eur J Pharmacol 674: 27-32.
108. O'Mahony SM, Bulmer DC, Coelho AM, Fitzgerald P, Bongiovanni C, Lee K, etal. (2010). 5-HT(2B) receptors modulate visceral hypersensitivity in a stress-sensitive animal model of brain-gut axis dysfunction. Neurogastroenterol Motil 22: 573-578.
109. Paizanis E, Renoir T, Lelievre V, Saurini F, Melfort M, Gabriel C, etal. (2010). Behavioural and neuroplastic effects of the new-generation antidepressant agomelatine compared to fluoxetine in glucocorticoid receptor-impaired mice. Int J Neuropsychopharmacol 13: 759-774.
110. Palucha A, Pilc A, (2007). Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs. Pharmacol Ther 115: 116-147.
111. Papp M, Gruca P, Boyer PA, Mocaer E, (2003). Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology 28: 694-703.
112. Papp M, Litwa E, Gruca P, Mocaer E, (2006). Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Behav Pharmacol 17: 9-18.
113. Paul IA, Skolnick P, (2003). Glutamate and depression: clinical and preclinical studies. Ann N Y Acad Sci 1003: 250-272.
114. Pei Q, Zetterstrom TS, Sprakes M, Tordera R, Sharp T, (2003). Antidepressant drug treatment induces Arc gene expression in the rat brain. Neuroscience 121: 975-982.
115. Pepin MC, Pothier F, Barden N, (1992a). Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression. Mol Pharmacol 42: 991-995.
116. Pepin MC, Pothier F, Barden N, (1992b). Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene. Nature 355: 725-728.
117. Perez J, Mori S, Caivano M, Popoli M, Zanardi R, Smeraldi E, etal. (1995). Effects of fluvoxamine on the protein phosphorylation system associated with rat neuronal microtubules. Eur Neuropsychopharmacol 5 (Suppl.): 65-69.
118. Pickard GE, Rea MA, (1997). Serotonergic innervation of the hypothalamic suprachiasmatic nucleus and photic regulation of circadian rhythms. Biol Cell 89: 513-523.
119. Pitrosky B, Kirsch R, Malan A, Mocaer E, Pevet P, (1999). Organization of rat circadian rhythms during daily infusion of melatonin or S20098, a melatonin agonist. Am J Physiol 277: R812-R828.
120. Qi X, Lin W, Li J, Li H, Wang W, Wang D, etal. (2008). Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiol Dis 31: 278-285.
121. Quera Salva MA, Vanier B, Laredo J, Hartley S, Chapotot F, Moulin C, etal. (2007). Major depressive disorder, sleep EEG and agomelatine: an open-label study. Int J Neuropsychopharmacol 10: 691-696.
122. Racagni G, Popoli M, Molteni R, Musazzi L, Calabrese F, Tardito D, etal. (2011). Mode of action of agomelatine: synergy between melatonergic and 5-HT2C receptors. World J Biol Psychiatry 12: 574-587.
123. Rainer Q, Xia L, Guilloux JP, Gabriel C, Mocaer E, Hen R, etal. (2012). Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int J Neuropsychopharmacol 15: 321-335.
124. Reagan LP, Reznikov LR, Evans AN, Gabriel C, Mocaer E, Fadel JR, (2012). The antidepressant agomelatine inhibits stress-mediated changes in amino acid efflux in the rat hippocampus and amygdala. Brain Res 1466: 91-98.
125. Redman JR, Francis AJ, (1998). Entrainment of rat circadian rhythms by the melatonin agonist S-20098 requires intact suprachiasmatic nuclei but not the pineal. J Biol Rhythms 13: 39-51.
126. Redman JR, Guardiola-Lemaitre B, Brown M, Delagrange P, Armstrong SM, (1995). Dose dependent effects of S-20098, a melatonin agonist, on direction of re-entrainment of rat circadian activity rhythms. Psychopharmacology (Berl) 118: 385-390.
127. Roybal K, Theobold D, Graham A, DiNieri JA, Russo SJ, Krishnan V, etal. (2007). Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci U S A 104: 6406-6411.
128. Schmelting B, Corbach-Sohle S, Kohlhause S, Schlumbohm C, Flugge G, Fuchs E, (2014). Agomelatine in the tree shrew model of depression: effects on stress-induced nocturnal hyperthermia and hormonal status. Eur Neuropsychopharmacol 24: 437-447.
129. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS, (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22: 3251-3261.
130. Soumier A, Banasr M, Lortet S, Masmejean F, Bernard N, Kerkerian-Le-Goff L, etal. (2009). Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus. Neuropsychopharmacology 34: 2390-2403.
131. Steardo L, Monteleone P, Trabace L, Cannizzaro C, Maj M, Cuomo V, (2000). Serotonergic modulation of rat pineal gland activity: in vivo evidence for a 5-Hydroxytryptamine(2C) receptor involvement. J Pharmacol Exp Ther 295: 266-273.
132. Tajes OM, Pelegri GC, Vilaplana HJ, Pallas LM, Camins EA, (2009). An evaluation of the neuroprotective effects of melatonin in an in vitro experimental model of age-induced neuronal apoptosis. J Pineal Res 46: 262-267.
133. Takahashi JS, (2004). Finding new CLOCK components: past and future. J Biol Rhythms 19: 339-347.
134. Taliaz D, Stall N, Dar DE, Zangen A, (2010). Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry 15: 80-92.
135. Taliaz D, Haramati S, Chen A, Zangen A, (2011). The role of brain-derived neurotrophic factor in the effect of antidepressant treatments. Society for Neuroscience Nov. 12-16, Washington DC: p 904.07 [itinerary planner].
136. Tang SW, Helmeste D, Leonard B, (2012). Is neurogenesis relevant in depression and in the mechanism of antidepressant drug action? A critical review. World J Biol Psychiatry 13: 402-412.
137. Tardito D, Milanese M, Bonifacino T, Musazzi L, Grilli M, Mallei A, etal. (2010). Blockade of stress-induced increase of glutamate release in the rat prefrontal/frontal cortex by agomelatine involves synergy between melatonergic and 5-HT2C receptor-dependent pathways. BMC Neurosci 11: 68.
138. Tordera RM, Pei Q, Sharp T, (2005). Evidence for increased expression of the vesicular glutamate transporter, VGLUT1, by a course of antidepressant treatment. J Neurochem 94: 875-883.
139. Tordera RM, Totterdell S, Wojcik SM, Brose N, Elizalde N, Lasheras B, etal. (2007). Enhanced anxiety, depressive-like behaviour and impaired recognition memory in mice with reduced expression of the vesicular glutamate transporter 1 (VGLUT1). Eur J Neurosci 25: 281-290.
140. Tuma J, Strubbe JH, Mocaer E, Koolhaas JM, (2005). Anxiolytic-like action of the antidepressant agomelatine (S 20098) after a social defeat requires the integrity of the SCN. Eur Neuropsychopharmacol 15: 545-555.
141. Turek FW, (2007). From circadian rhythms to CLOCK genes in depression. Int Clin Psychopharmacol 22 (Suppl. 2): S1-S8.
142. Turek FW, Scarbrough K, Penev P, Labyak S, Valentinuzzi VS, Van Reeth O, (2001) Aging of the mammalian circadian system. In:, Takahashi JS, Turek FW, Moore RY, (eds). Circadian Clocks. Kluwer Academic/Plenum Publishers: New York, pp. 292-317.
143. Uezato A, Meador-Woodruff JH, McCullumsmith RE, (2009). Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia. Bipolar Disord 11: 711-725.
144. Van Reeth O, Olivares E, Zhang Y, Zee PC, Mocaer E, Defrance R, etal. (1997). Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters. Brain Res 762: 185-194.
145. Van Reeth O, Olivares E, Turek FW, Granjon L, Mocaer E, (1998). Resynchronisation of a diurnal rodent circadian clock accelerated by a melatonin agonist. Neuroreport 9: 1901-1905.
146. Van Reeth O, Weibel L, Olivares E, Maccari S, Mocaer E, Turek FW, (2001). Melatonin or a melatonin agonist corrects age-related changes in circadian response to environmental stimulus. Am J Physiol Regul Integr Comp Physiol 280: R1582-R1591.
147. Varcoe TJ, Salked M, Mocaer E, Seguin L, Kennaway DJ, (2009). Effects of chronic agomelatine administration on the expression of a panel of genes in various brain areas of rats. Eur Neuropsychopharmacol 19: S440.
148. Wang LM, Dragich JM, Kudo T, Odom IH, Welsh DK, O'Dell TJ, etal. (2009). Expression of the circadian CLOCK gene Period2 in the hippocampus: possible implications for synaptic plasticity and learned behaviour. ASN Neuro 1: 139-152.
149. Watts SW, Fink GD, (1999). 5-HT2B-receptor antagonist LY-272015 is antihypertensive in DOCA-salt-hypertensive rats. Am J Physiol 276: H944-H952.
150. Weibel L, Turek FW, Mocaer E, Van Reeth O, (2000). A melatonin agonist facilitates circadian resynchronization in old hamsters after abrupt shifts in the light-dark cycle. Brain Res 880: 207-211.
151. Weil ZM, Hotchkiss AK, Gatien ML, Pieke-Dahl S, Nelson RJ, (2006). Melatonin receptor (MT1) knockout mice display depression-like behaviors and deficits in sensorimotor gating. Brain Res Bull 68: 425-429.
152. Werry TD, Loiacono R, Sexton PM, Christopoulos A, (2008). RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol Ther 119: 7-23.
153. Wirz-Justice A, Van den Hoofdakker RH, (1999). Sleep deprivation in depression: what do we know, where do we go? Biol Psychiatry 46: 445-453.
154. Ying SW, Rusak B, Delagrange P, Mocaer E, Renard P, Guardiola-Lemaitre B,
155. Ying SW, Rusak B, Mocaer E, (1998). Chronic exposure to melatonin receptor agonists does not alter their effects on suprachiasmatic nucleus neurons. Eur J Pharmacol 342: 29-37.
156. Yous S, Andrieux J, Howell HE, Morgan PJ, Renard P, Pfeiffer B, etal. (1992). Novel naphthalenic ligands with high affinity for the melatonin receptor. J Med Chem 35: 1484-1486.
157. Zink M, Vollmayr B, Gebicke-Haerter PJ, Henn FA, (2010). Reduced expression of glutamate transporters vGluT1, EAAT2 and EAAT4 in learned helpless rats, an animal model of depression. Neuropharmacology 58: 465-473.