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Wednesday, May 6, 2015

AGOMELATINE - A Powerful Anti-Depressant that Alleviates Insomnia, Balances Circadian Rhythms and Enhances Dopamine Activity

This article has been exclusively written for TrueLIFE Research - and to foster further progress within serotonergic neuron research and in establishing a basis for legitimate research with the viable compound  AGOMELATINE

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Agomelatine is a novel and extremely valuable addition to the anti-depressant class of drugs. Agomelatine has a superior safety profile and very 'clean' mechanism of action.

It is a  melatonin receptor agonist (MT1 (Ki=0.1nM) and MT2 (Ki=0.12nM)) and a 5-HT2C (Ki=631nM) receptor antagonist.[1]

It is highly efficacious at the target dose of 25mg, but it is often well-tolerated for more depressed or sleep deprived individuals at the dosage of 50 mg[2].

Agomelatine has shown improvements in both youthful [3] and elderly patients[4] [5], and has the added benefit of normalizing sleep cycles / circadian rhythms[6]. A pooled analysis and four randomized clinical trials state that agomelatine is better tolerated overall than SSRI's [7] and another study shows that it does not cause sexual side-effects[8]. It is thus seen as an age-friendly, characteristically safe anti-depressant on multiple levels with a very balanced effect.


Agomelatine is specifically a melatonergic agonist[9], that means it essentially acts at specific melatonin receptors and thus balances the sleep-wake cycle...perpetuating the ability to sleep at night and waking up refreshed. Because of this property, it can improve neurological and hormonal parameter's and improve depression and occurrences of some forms of anxiety resultant from deficits in sleep or inverted circadian cycles[10]

Agomelatine is additionally a serotonin 2C antagonist[11], this essentially will lessen/inhibit the ability of serotonin to interact with that receptor and as a result - the constitutive activity is lessened from. When antagonized, dopamine release is provoked due to signal disinhibition. This essentially means that agomelatine can raise dopamine levels and can improve quality of life. It is reported to significantly improve anhedonia that is caused by SSRI's and other serotonergic agents as well as anhedonia from other causes[12][13][14].

Norepinephrine may also be disinhibited by this mode of action, which can theoretically improve sensory arousal deficits; such as decreased sense of smell, vigilance and hearing. It may improve perception of quality of life and general energy levels[15].

By modulating the above neurotransmitters, this agent can be very effective in providing a comprehensive attack on depression and anxiety. But most importantly, it has become an extremely novel and important agent in the research of circadian rhythms and the treatment of sleep-wake disorders of various etiology. As we have gone past a "glance" at melatonin's involvement, and instead moved to the next phase in clinical settings - quality of life can improve, and the future is charted for further developments that may be groundbreaking in sleep studies and disorders[16][17].

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