Agomelatine
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| File:Agomelatine.svg | |
| File:Agomelatine-from-xtal-1994-CM-3D-balls.png | |
| Systematic (IUPAC) name | |
|---|---|
|
N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide | |
| Clinical data | |
| [[Regulation of therapeutic goods |Template:Engvar data]] | |
| Routes of administration | Oral |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | <5% [1] |
| Metabolism | hepatic (90%CYP1A2;10%CYP2C9) |
| Biological half-life | < 2 h |
| Identifiers | |
| CAS Number | 138112-76-2 |
| ATC code | N06AX22 (WHO) |
| PubChem | CID 82148 |
| IUPHAR/BPS | 198 |
| ChemSpider | 74141 |
| Chemical data | |
| Formula | C15H17NO2 |
| Molar mass | 243.301[[Script error: No such module "String".]] |
| Script error: No such module "collapsible list". | |
Agomelatine (trade names Valdoxan, Melitor, Thymanax) is an antidepressant developed by the pharmaceutical company Servier. It is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor.[2] Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of 5-HT2C results in an enhancement of DA and NE release and activity of frontocortical dopaminergic and adrenergic pathways.[3][4] Agomelatine is also a potent agonist at melatonin receptors which makes it the first melatonergic antidepressant.[4][5] Agomelatine has not been associated with weight gain, sexual side effects, sleep problems or withdrawal syndrome; this is in contrast to most older antidepressants such as SSRIs.[6][7]
Studies
Although some controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression[8], there are unpublished randomised controlled trials that have failed to show that agomelatine is more effective than placebo[9][9]. Agomelatine appears to cause fewer sexual side effects and discontinuation effects than sertraline and paroxetine. Additionally, possibly because of its action on melatonin receptors, agomelatine appears to improve sleep quality, with no reported daytime drowsiness[7]. Agomelatine has demonstrated anxiolytic properties in rodents[10]. Its efficacy in generalised anxiety disorder has been assessed by Stein et al (2008) who reported it significantly more effective than placebo treatment.[11]
Development
Agomelatine was discovered and developed by the European pharmaceutical company Servier Laboratories Ltd. Servier continued to develop the drug and conduct phase III trials in the European Union. In March 2005 Servier submitted agomelatine to the European Medicines Agency (EMEA) under the trade names Valdoxan and Thymanax.[12] 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 (agomelatine). The major concern was that efficacy had not been sufficiently shown. The CHMP had no special concerns about the side effects.[12] In September 2007, Servier submitted a new marketing application for Valdoxan (agomelatine) to the EMEA.[13] On 20 November 2008, Valdoxan was given a positive opinion, with restrictions,[14] by the EMEA[13], and was subsequently given marketing authorisation in the European Union on 20 February 2009.[15] Release dates for agomelatine will depend on marketing arrangements in the individual countries of the EU.
In March 2006, Servier announced it had sold the rights to market agomelatine in the United States to Novartis.[16] Agomelatine is currently undergoing phase III clinical trials in the US.[17]
Novartis currently lists the drug as scheduled for submission to the FDA no earlier than 2012.
Structure
The chemical structure of agomelatine is very similar to that of melatonin. Where melatonin has an NH group, agomelatine has an HC=CH group. Thus melatonin contains an indole part, whereas agomelatine has a naphthalene bioisostere instead.[18]
References
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<references />, or <references group="..." />External links
- Agomelatine Psychonauts Google Group
- 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
- Clinical trial data in the United Kingdom via the NHS' National electronic Library of Medicines (NeLM)
- Clinical trial data in the United States via ClinicalTrials.gov
it:Agomelatina nl:Agomelatine pl:Agomelatyna pt:Agomelatina fi:Agomelatiini
sv:Agomelatin- ↑ www.emea.europa.eu/
- ↑ "Valdoxan or Agomelatine for Depression". Health and Life.
- ↑ Int J Neuropsychopharmacol. 2007 Oct;10(5):575-8. Epub 2007 Aug 6. PMID: 17681087
- ↑ 4.0 4.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Valdoxan: A Unique Mode of Action Valdoxan.com. Servier. Last accessed 6 July 2009.
- ↑ Montgomery, Stuart (12 October 2006). "Major depressive disorders: clinical efficacy and tolerability of agomelatine, a new melatonergic agonist" (PDF). European Neuropsychopharmacology. Retrieved 6 July 2009.
- ↑ 7.0 7.1 "Valdoxan: A New Approach to The Treatment of Depression". Medical News Today. MediLexicon International Ltd. 2005-04-05. Retrieved 14 May 2009.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ 9.0 9.1 Howland, Robert (2009-11-16). "Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults" (PDF). Neuropsychiatric Disease and Treatment. United Kingdom: Dove Medical Press. 5: 563–576. PMC 2785860 Freely accessible. PMID 19966905. Retrieved 2010-01-19.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Stein, D.; Ahokas, A.; De Bodinat, C. (2008). "Efficacy of agomelatine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study". Journal of clinical psychopharmacology. 28 (5): 561–566. doi:10.1097/JCP.0b013e318184ff5b. PMID 18794654.
- ↑ 12.0 12.1 "Questions and Answers on Recommendation for Refusal of Marketing Authorisation" (PDF). European Medicines Agency. 18 November 2006. Retrieved 6 July 2009.
- ↑ 13.0 13.1 "CHMP Assessment Report for Valdoxan" (PDF). European Medicines Agency. 20 November 2008. Retrieved 6 July 2009.
- ↑ Transaminases elavations and interactions with potent CYP 1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin]
- ↑ "VALDOXAN (AGOMELATINE), A NOVEL ANTIDEPRESSANT, RECEIVES EUROPEAN MARKETING AUTHORISATION". Servier UK. 25 February 2009. Retrieved 6 July 2009.
- ↑ Bentham, Clara (2006-03-29). "Servier and Novartis sign licensing agreement for agomelatine, a novel treatment for depression". Servier UK. Retrieved 2009-05-15.
- ↑ "Clinical trials for agomelatine". ClinicalTrials.gov. National Institutes of Health. Retrieved 6 July 2009.
- ↑ Tinant, B.; Declercq, J. P.; Poupaert, J. H.; Yous, S.; Lesieur, D. (1994). "N-[2-(7-Methoxy-1-naphthyl)ethyl]acetamide, a potent melatonin analog". Acta Cryst. C. 50: 907–910. doi:10.1107/S0108270193012922.
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