Agomelatine

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. Agomelatine showed significant benefits over paroxetine due to the complete absence of side effects including the associated sexual side effects that are troublesome with some antidepressants. Because of its action upon the melatonin receptors, agomelatine shows a marked improvement in 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.