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Chemical Compound Review

Thymanax     N-[2-(7-methoxynaphthalen-1...

Synonyms: Valdoxan, Melitor, Agomelatine, Valdoxan (TN), AGO-178, ...
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Disease relevance of Agomelatine


Psychiatry related information on Agomelatine


High impact information on Agomelatine

  • Here, we determined the effects of agomelatine (S-20098), a new antidepressant, on various phases of neurogenesis in the dentate gyrus of adult rat [11].
  • RESULTS: Chronic (3 weeks) but not acute (4 hours) or subchronic (1 week) administration of agomelatine increased cell proliferation and neurogenesis in the ventral dentate gyrus, a region notably implicated in response to emotion, which is consistent with the antidepressant-anxiolytic properties of the drug [11].
  • In contrast, the agonist of the Mel(1b) receptor, S-20098 (Servier, Paris, France), produced singlet oxygen with a quantum efficiency of psidelta = 0.34 [12].
  • In contrast to the reference compounds, melatonin, agomelatine (S 20098), and N-[2-(2, 7-dimethoxynaphth-1-yl)ethyl]acetamide, which were very potent at lightening the skin of X. laevis tadpoles, compounds 4a-c were inactive or weakly active (EC50 > 1 microM) [13].
  • Previous studies showed that agomelatine is able to restore disrupted circadian rhythms, which were implicated in the pathophysiology of seasonal affective disorder (SAD) [6].

Biological context of Agomelatine


Anatomical context of Agomelatine

  • Extending agomelatine treatment over several weeks, however, increases survival of newly formed neurons in the entire dentate gyrus [11].
  • Neither acute nor chronic treatment with agomelatine (10 mg/kg i.p. for 14 days or 50 mg/kg i.p. for 21 days) changed the density of 5-HT(1A) receptors and their coupling with G proteins in the DRN and the hippocampus in rats [18].
  • Because functional desensitization of 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) occurs after chronic administration of several classes of antidepressants, we investigated whether this adaptive change could also be induced by agomelatine [18].
  • Extracellular levels of noradrenaline in frontal cortex were also dose dependently enhanced by agomelatine in parallel with an acceleration in the firing rate of adrenergic cell bodies in the locus coeruleus [19].
  • Furthermore, agomelatine dose dependently enhanced dialysis levels of dopamine in frontal cortex of freely moving rats, whereas they were unaffected in nucleus accumbens and striatum [19].

Associations of Agomelatine with other chemical compounds


Gene context of Agomelatine


Analytical, diagnostic and therapeutic context of Agomelatine


  1. Melatonin receptors in human uveal melanocytes and melanoma cells. Roberts, J.E., Wiechmann, A.F., Hu, D.N. J. Pineal Res. (2000) [Pubmed]
  2. Efficacy and tolerance profile of agomelatine and practical use in depressed patients. Rouillon, F. International clinical psychopharmacology. (2006) [Pubmed]
  3. Successful use of S20098 and melatonin in an animal model of delayed sleep-phase syndrome (DSPS). Armstrong, S.M., McNulty, O.M., Guardiola-Lemaitre, B., Redman, J.R. Pharmacol. Biochem. Behav. (1993) [Pubmed]
  4. Melatonin and its new agonist S-20098 restore synchronized sleep fragmented by experimental trypanosome infection in the rat. Grassi-Zucconi, G., Semprevivo, M., Mocaer, E., Kristensson, K., Bentivoglio, M. Brain Res. Bull. (1996) [Pubmed]
  5. RNA expression of human telomerase subunits TR and TERT is differentially affected by melatonin receptor agonists in the MCF-7 tumor cell line. Leon-Blanco, M.M., Guerrero, J.M., Reiter, R.J., Pozo, D. Cancer Lett. (2004) [Pubmed]
  6. Agomelatine in the treatment of seasonal affective disorder. Pjrek, E., Winkler, D., Konstantinidis, A., Willeit, M., Praschak-Rieder, N., Kasper, S. Psychopharmacology (Berl.) (2007) [Pubmed]
  7. Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Millan, M.J., Brocco, M., Gobert, A., Dekeyne, A. Psychopharmacology (Berl.) (2005) [Pubmed]
  8. Biological rhythm disturbances in mood disorders. Wirz-Justice, A. International clinical psychopharmacology. (2006) [Pubmed]
  9. Major depressive disorders: clinical efficacy and tolerability of agomelatine, a new melatonergic agonist. Montgomery, S.A. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2006) [Pubmed]
  10. Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters. Van Reeth, O., Olivares, E., Zhang, Y., Zee, P.C., Mocaer, E., Defrance, R., Turek, F.W. Brain Res. (1997) [Pubmed]
  11. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Banasr, M., Soumier, A., Hery, M., Mocaër, E., Daszuta, A. Biol. Psychiatry (2006) [Pubmed]
  12. Photophysical studies on melatonin and its receptor agonists. Roberts, J.E., Hu, D.N., Martinez, L., Chignell, C.F. J. Pineal Res. (2000) [Pubmed]
  13. Melatonergic properties of the (+)- and (-)-enantiomers of N-(4-methoxy-2,3-dihydro-1H-phenalen-2-yl)amide derivatives. Jellimann, C., Mathé-Allainmat, M., Andrieux, J., Renard, P., Delagrange, P., Langlois, M. J. Med. Chem. (1999) [Pubmed]
  14. Agomelatine(S 20098) antagonizes the penile erections induced by the stimulation of 5-HT2C receptors in Wistar rats. Chagraoui, A., Protais, P., Filloux, T., Mocaër, E. Psychopharmacology (Berl.) (2003) [Pubmed]
  15. 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. Leproult, R., Van Onderbergen, A., L'hermite-Balériaux, M., Van Cauter, E., Copinschi, G. Clin. Endocrinol. (Oxf) (2005) [Pubmed]
  16. Microdialysis: an alternative for in vitro and in vivo protein binding studies. Le Quellec, A., Dupin, S., Tufenkji, A.E., Genissel, P., Houin, G. Pharm. Res. (1994) [Pubmed]
  17. Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis. Cajochen, C., Kräuchi, K., Möri, D., Graw, P., Wirz-Justice, A. Am. J. Physiol. (1997) [Pubmed]
  18. Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain. Hanoun, N., Mocaër, E., Boyer, P.A., Hamon, M., Lanfumey, L. Neuropharmacology (2004) [Pubmed]
  19. 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. Millan, M.J., Gobert, A., Lejeune, F., Dekeyne, A., Newman-Tancredi, A., Pasteau, V., Rivet, J.M., Cussac, D. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  20. Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Dubocovich, M.L., Masana, M.I., Iacob, S., Sauri, D.M. Naunyn Schmiedebergs Arch. Pharmacol. (1997) [Pubmed]
  21. Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. Barden, N., Shink, E., Labbé, M., Vacher, R., Rochford, J., Mocaër, E. Prog. Neuropsychopharmacol. Biol. Psychiatry (2005) [Pubmed]
  22. Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats. Loiseau, F., Le Bihan, C., Hamon, M., Thiébot, M.H. Psychopharmacology (Berl.) (2005) [Pubmed]
  23. Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Papp, M., Litwa, E., Gruca, P., Mocaër, E. Behavioural pharmacology. (2006) [Pubmed]
  24. Entrainment of circadian rhythms by S-20098, a melatonin agonist, is dose and plasma concentration dependent. Martinet, L., Guardiola-Lemaitre, B., Mocaer, E. Pharmacol. Biochem. Behav. (1996) [Pubmed]
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