property agomelatine shares with several atypical antipsychotics, such as aripiprazole, which are themselves used as atypical antidepressants. 5-HT2B antagonists are currently being investigated for their usefulness in reducing cardiotoxicity of drugs as well as being effective in reducing headache. Hence this particular receptor antagonism of agomelatine is useful for its antidepressant effectiveness as well as reducing the drug's adverse effects. Chemistry Structure The chemical structure of agomelatine is very similar to that of melatonin. Where melatonin has an indole ring system, agomelatine has a naphthalene bioisostere instead. Synthesis History 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 (EMA) under the trade names Valdoxan and Thymanax. On 27 July 2006, the Committee for Medical Products for Human Use (CHMP) of the EMA recommended a refusal of the marketing authorisation. The major concern was that efficacy had not been sufficiently shown, while there were no special concerns about side effects. In September 2007, Servier submitted a new marketing application to the EMA. In March 2006, Servier announced it had sold the rights to market agomelatine in the United States to Novartis. It was undergoing several phase III clinical trials in the US, and until October 2011 Novartis listed the drug as scheduled for submission to the FDA no earlier than 2012. However, the development for the US market was discontinued in October 2011, when the results from the last of those trials became available. It received approval from the European Medicines Agency (EMA) for marketing in the European Union in February 2009 and approval from the Therapeutic Goods Administration (TGA) for marketing in Australia in August 2010. Research Circadian rhythm sleep disorders Agomelatine has been investigated for its effects on sleep regulation due its actions as a melatonin receptor agonist. Studies report various improvements in general quality of sleep metrics, as well as benefits in circadian rhythm sleep disorders. However, research is very limited (e.g., case reports) and agomelatine is not approved for use in the treatment of sleep disorders. Seasonal affective disorder A 2019 Cochrane review suggested no recommendations of agomelatine in support of, or against, its use to treat individuals with seasonal affective disorder. References External links Genf interaction table- https://www.hug.ch/sites/interhug/files/structures/pharmacologie_et_toxicologie_cliniques/carte_cytochromes_2016_final.pdf 5-HT2C antagonists Acetamides Antidepressants Laboratoires Servier Melatonin receptor