Agomelatine(阿戈美拉汀)
Monoisotopic: 243.125928793
Agomelatine 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. 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. In 2006 Servier sold the rights to develop Agomelatine in the US to Novartis.
The development for the US market was discontinued in October 2011. It is currently sold in Australia under the Valdoxan trade name.
| Synthesis Reference | Not Available |
| General Reference |
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| Type | small molecule |
| Classes | Not Available |
| Substructures | Not Available |
| Indication | Agomelatine is indicated for the treatment of major depressive episodes in adults. |
| Pharmacodynamics | Agomelatine resynchronises circadian rhythms in animal models of delayed sleep phase syndrome and other circadian rhythm disruptions. It increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin. Agomelatine has shown an antidepressant-like effect in animal models of depression (learned helplessness test, despair test, chronic mild stress) as well as in models with circadian rhythm desynchronisation and in models related to stress and anxiety. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset. Controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression |
| Mechanism of action | The novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors (MT1 and MT2) and as an antagonist at serotonin (5-HT)(2C) receptors. |
| Absorption | Bioavailability is less than 5%. |
| Volume of distribution | Not Available |
| Protein binding | > 95% |
| Metabolism |
Hepatic (90% CYP1A2 and 10% CYP2C9).
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| Route of elimination | Not Available |
| Half life | <2 hours |
| Clearance | Not Available |
| Toxicity | Not Available |
| Affected organisms | Not Available |
| Pathways | Not Available |
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| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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