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Agomelatine chemical structure
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|Elimination half-life||2.3hours ?|
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Agomelatine (Valdoxan, Melitor, Thymanax) is a chemical compound that is structurally closely related to melatonin. Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors, tested in an animal model of depression (forced swimming test in rodents). It is concluded that the antidepressant-like activity in this model most probably involves a combination of both its melatonin agonist and 5-HT2C receptor antagonist properties.
Controlled studies with humans have shown that agomelatine is comparable to paroxetine in treatment of major depression, in that both have similar efficacy rates. Agomelatine, however, may have an advantage over paroxetine due to having significantly less side effects including the associated sexual side effects that are troublesome with some antidepressants. Because of its action upon the melatonin receptors, agomelatine may also improve sleep quality. However unlike other antidepressants with sedative effects there were no associated instances of daytime drowsiness.
Agomelatine has also proven to have anxiolytic properties and thus may prove to be very useful in the treatment of anxiety disorders.  Recently studies have shown Agomelatine to be superior to the SSRI antidepressant Sertraline for treatment of major depressive disorder. With noted improvements in the HAM-D, and HAM-A scales compaired to Sertraline. A lower rate of discontinuation was also seen with Agomelatine. 
Agomelatine was discovered and developed by the European pharmaceutical company Servier Laboratories Ltd. Servier continue to develop the drug and conduct phase III trials in the European Union. In 2005 Servier submitted agomelatine to the European Medicines Agency (EMEA). On 27 July 2006 the Committee for Medical Products for Human Use (CHMP) of the EMEA recommended a refusal of the marketing authorisation of Valdoxan/Thymanax. The major concern was that efficacy had not been sufficiently shown. The CHMP had no special concerns about the side effects. As of November 2007 (estimated) Servier has resubmitted Agomelatine to the EMEA. EMEA approved the drug in November 2008.
In 2006 Servier sold the rights to develop Agomelatine in the US to Novartis. According to the pipeline page on Novartis.com, the company plans to file a New Drug Application (NDA) for agomelatine (AGO178) with the Food and Drug Administration (FDA) in 2008. 
- ↑ M. J. Millan, A. Gobert, F. Lejeune, A. Dekeyne, A. Newman-Tancredi, V. Pasteau, J.-M. Rivet & D. Cussac (September 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. The Journal of Pharmacology and Experimental Therapeutics 306 (3): 954–954.
- ↑ Agomelatine ( Valdoxan )
- ↑ Agomelatine ( Valdoxan ) : an anxiolytic antidepressant
- ↑ http://www.docguide.com/news/content.nsf/news/852571020057CCF6852574B8006445A8
- ↑ Questions and answers http://www.emea.europa.eu/humandocs/PDFs/EPAR/valdoxan/H-656-657-RQ&A-en.pdf
- ↑ http://www.emea.europa.eu/pdfs/human/press/pr/60656608en.pdf
- ↑ Servier UK | Public News | Servier and Novartis sign licensing agreement for agomelatine, a novel treatment for depression
- ↑ Products in Development http://www.novartis.com/research/products-in-development.shtml
- Novartis pipeline
- Major depressive disorders: clinical efficacy and tolerability of agomelatine, a new melatonergic agonist
- Remitted Depressed Patients Experience Less Sexual Dysfunction with Agomelatine (Valdoxan) than with Venlafaxine XR (Effexor XR): Presented at CPA
- Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors
- 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
- Agomelatine treatment has promising results in transgenic murine model
- Agomelatine: A New Treatment For Depression
- Phase III trial data November 2007 http://www.nelm.nhs.uk/Record%20Viewing/viewRecord.aspx?id=587059
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