AGOMELATINE

Product information

AGOMELATINE Basic information

Antidepressants Pharmacological effects Health risk Patent cases Application

Product Name:	AGOMELATINE
Synonyms:	AGOMELATINE;n-(2-(7-methoxy-1-naphthalenyl)ethyl)-acetamid;n-(2-(7-methoxy-1-naphthalenyl)ethyl)acetamide;n-(2-(7-methoxynaphth-1-yl)ethyl)acetamide;S20098,N-[2-(7-Methoxynaphth-1-yl)ethyl]acetamide;S 20098;AGOMELATIN;Acetamide, N-(2-(7-methoxy-1-naphthalenyl)ethyl)-
CAS:	138112-76-2
MF:	C15H17NO2
MW:	243.30098
EINECS:
Product Categories:	Aromatics Compounds;Aromatics;Neurochemicals;APIS;API;Agomelatine;Valdoxan, Melitor, Thymanax
Mol File:	138112-76-2.mol

AGOMELATINE Chemical Properties

mp	107-109°C
storage temp.	-20°C Freezer
CAS DataBase Reference	138112-76-2(CAS DataBase Reference)

Safety Information

Hazard Codes	N
Risk Statements	50
Safety Statements	61

 

AGOMELATINE Usage And Synthesis

Antidepressants	Agomelatine, which is developed by the French Servier company, is the world's first melatonin receptors MT1 and MT2 agonist class of antidepressants. It applies to the treatment of adult patients with severe depressive. We know that melatonin is an endogenous neural hormones. It is only produced by the pineal gland anterior pituitary at night, and acts on the melatonin receptor that focuses on the presence of hypothalamic suprachiasmatic nucleus (SCN). It is involved in mediating the circadian rhythms in mammals. It is the well-known time guardian in the body, which can regulate the biological clock that is modulated by external circadian cycle. However, since that melatonin has high catabolism rate in vivo which mikes its half-life shorter and the selectivity of its receptor located in the SCN poorer, the treatment of circadian rhythms disorders is limited. Therefore, in order to overcome these drawbacks of melatonin, the researchers designed a series of melatonin analogues. Molecular modeling studies have shown that indole ring of melatonin is the structure sites of catabolic inactivation. Indole ring is an ideal site of isosteric modifications. Agomelatine developed by Servier company is melatonin’s naphthalene biological (electronic) isostere analogs. Indole ring is substituted by naphthalene nucleus, which leads it have more metabolic stability than melatonin.
Pharmacological effects	The listing of agomelatine is a new breakthrough in the field of the treatment of depression. It is melatonin MT1 / MT2 receptor agonist and serotonin 2c (5-HT2C) receptor antagonist. It can make depressed patients’ biological rhythm disorders return to normal through the synergy between the two and then result in antidepressant efficacy. Its unique mechanism of action has opened up an innovative way to treat depression. Agomelatine’s mechanism of drug action is completely different with antidepressants that are commonly used today, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI). SSRI and SNRI antidepressants achieve antidepressant efficacy by increasing concentration of serotonin. But it also brings a lot of side effects, such as weight changes, sexual dysfunction, withdrawal syndrome and the like. The molecular structure of agomelatine directly combines with serotonin 2c (5HT2c) receptor of post-synaptic membrane so as to exert its antidepressant efficacy without increasing serotonin concentration in the synaptic cleft. This unique mechanism of action makes agomelatine quickly and effectively exert its antidepressant efficacy at the same time, and avoid the occurrence of adverse drug reactions to an extreme. Another unique targets of agomelatine is in melatonin receptors. MT1 and MT2 receptors densely distribute in the human suprachiasmatic nucleus. The nucleus mainly control human sleep rhythm. Agomelatine can well improve the quality of patients’ sleep by agonism on MT1 MT2 receptors, and improve patients’ wakefulness during the day. The quality of sleep has both cause and effect relationship with depression outcomes state. It is reported that 80% of patients with depression have the problems of sleep disorders at different levels. The improvement of sleep quality can directly contribute to the improvement of the overall clinical condition of patients with depression. The above information is edited by the Chemicalbook of Ge Qian.
Health risk	October 30, 2012, the British Medicines and Healthcare Products Agency (MHRA) released agomelatine (agomelatine, Valdoxan/Thymanax) security information. MHRA found that several cases appears serious reports of liver toxicity with agomelatine, including six cases of liver failure patients within worldwide report. Agomelatine's drug information already includes in the recommendations that all patients need liver function tests at the start of treatment and during treatment. Now liver function tests should also be recommended when the drug dose is increased. MHRA recommends that if the patients have potential liver damage symptoms or signs, or that the increases of serum transaminase beyond the upper limit of normal (ULN) three times is found in the function tests, it should be immediately suspended.
Patent cases	The earliest agomelatine compound patent is French Patent FR902393, which is applied in February 27, 1990. This patent has the same patent family in Europe, USA, Canada, Japan and Australia. But there is no Chinese patent. The above patents were all authorized after January 1, 1993. Therefore China is also ineligible for administrative protection. Agomelatine has both technology patent and polymorph patent in China. But it also can be avoided.
Application	Melatonin drugs.
Chemical Properties	White Solid
Usage	Agomelatine is an antidepressant drug. It is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of
Usage	Agomelatine is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. Agomelatine (S20098) displayed pKi values of 6.4 and 6.2 at native (porcine) and cloned, human (h)5-hydroxytryptamine (5-HT)2C receptors, respectively.

 

Company information

 Henan sunlake enterprise corporation is located in Henan Province , The central plain of China , Which enjoys favorable geogeaphical position and convenient transportion, The com[any was established in june. 1998 , until now having more than 18 years experience in manufacturing & exporting chemical raw material .

  Sunlake is a professional manufacturer engaged in producing and selling chemicals,including Organic & inorganic chemicals , pigments & Dyestuffs ,  Water treatment chemicals , Food & FEED additives and others . these products have been being well exported to europe , southeast Asia , the Middle East ,  Africa , South America and some other countries and areas.

    We sincerely welcome foreign friends to visit our plant for cooperation. With the idea of "quality first,credit priority, Excellent service", We are highly acknowledged by customers for good quality and competitive price. More importantly , the company has a strong R & D team, who are professional engineers and scholars with Ph. D. .So we are confident to serve you  better with our high - quality products and professional team.

    We are taking great efforts to provide our customers with demanded goods and professional services, and continuously improve our core ability of competition and get the momentum for sustainable development, and finally make us being a reliable and professional wupplier in international market.

    We  welcome any serious inquiries from all customers of the world, and sincerely hope to cooperate.