Agomelatine

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Agomelatine is an agonist of the melatonin receptors (MT1 and MT2) and an antagonist of the serotonin receptors (5HTC). Agomelatine was initially developed in 1997 and was granted authorization for medical use in the European Union in 2009 and in Australia in 2010.

Multiple trials have shown that Agomelatine may have effects on depressive symptoms. Agomelatine has also shown its potential efficacy in preventing the relapse of depression. Plus, it has demonstrated potential good tolerability compared with widely used antidepressants.

On the basis of favorable results in multiple clinical trials, Agomelatine was approved for medical use in Europe in 2009. A year later, this prescription compound was granted marketing authorization in Australia. However, the Food and Drug Administration (FDA) has yet to approve it.

Note: PureRawz sells Agomelatine for laboratory research use only.

Chemical Properties of Agomelatine

Working Mechanism of Agomelatine

Agomelatine binds with melatonin receptors (MT1 and MT2) to potentially stimulate the release of melatonin. It may also stop the action of serotonin receptors (5HTC), which could stimulate the release of norepinephrine and dopamine (it would not affect serotonin levels).

Its mechanisms of action are different from those of existing antidepressants. While Agomelatine could primarily act via the melatonergic and serotonergic pathways, most antidepressants you see on the market act via monoaminergic (monoamine) mechanisms.

This difference in their working mechanisms is noteworthy. A report prepared by the European Medicines Agency (EMA), as well as a meta-analysis of 20 trials, indicates that Agomelatine poses a relatively small risk of potentially severe side effects, as opposed to standard antidepressants.

Research Findings on Agomelatine

Multiple large-scale, randomized clinical trials have been conducted on Agomelatine. This research chemical has also attracted numerous animal and cell-based studies. All these trials and studies have demonstrated that Agomelatine possesses enormous potential as an antidepressant.

Agomelatine and Major Depressive Disorder

Ten placebo-controlled trials were conducted to investigate the short-term efficacy of Agomelatine in major depressive disorder in adult subjects. At the end of the trials (over 6 or 8 weeks), Agomelatine demonstrated potential significant efficacy in 6 out of the ten trials.

A meta-analysis of 20 trials with more than 7,400 participants concluded that Agomelatine is a potentially effective antidepressant with similar efficacy to standard antidepressants. The trials’ results also show that Agomelatine may pose a relatively small risk of sexual side effects.

Another placebo-controlled trial demonstrated that Agomelatine could potentially successfully prevent relapse in more than two-thirds (78%) of the patients. The incidence of relapse during the 6-month follow-up period was potentially 22% and 47% for Agomelatine and placebo, respectively.

Agomelatine and Anxiety

A 2005 study found that Agomelatine may potentially elicit anxiety-relieving properties in rats. The anxiolytic effects produced by Agomelatine were comparable to those induced by clorazepate, a clinically approved compound to treat anxiety, even though Agomelatine had a different mechanism of action.

A relatively recent study has demonstrated how Agomelatine can potentially relieve anxiety. It has been shown that Agomelatine blocks a receptor in nerve cells (5HT2C), which could potentially play a role in causing anxiety. In addition, Agomelatine may activate the MT receptor, which is known for keeping anxiety in check.

The researchers also concluded that Agomelatine’s potential anxiolytic effects are caused by mechanisms that are distinct from those of other non-controlled prescription drugs currently used to treat General Anxiety Disorder (GAD).

Agomelatine and Cognition

In a 2017 animal study, Agomelatine was effective in alleviating stress-induced cognitive impairments in mice. This research chemical was also shown to reverse gene-related effects of stress. Plus, Agomelatine significantly reversed the memory impairments caused by stress in mice.

Another study was conducted to investigate the chronic effects of Agomelatine administration on the cognitive performance of rats. It was noted that the memory performance of rats during one of the study’s trials was significantly better than that of the controls.

In addition, Agomelatine-treated animals achieved a better learning index. These data provide evidence that Agomelatine has beneficial effects on the cognitive parameters of animals.

Agomelatine and Sleep

An analysis of the effects of Agomelatine on sleep indicates that this antidepressant produces subjective and objective potential improvements in sleep. Agomelatine may potentially increase slow-wave sleep and improve sleep wave quality, with little to no effect whatsoever on REM sleep.It has also been shown that when taken at night, Agomelatine could potentially improve sleep patterns by mimicking the natural rhythm of melatonin release in test models. Furthermore, it can have the potential ability to restore non-rapid-eye movement (NREM-REM) sleep stage cycles within nighttime sleep.

Agomelatine has also been shown to have the potential to improve all aspects of the sleep-wake cycle in depressed models. This antidepressant has demonstrated a potential improvement in sleep patterns and focus.

Agomelatine and Autism

Agomelatine has shown an ameliorative effect on behavioral, neurochemical, and blood-brain barrier alterations in animals with an induced autism spectrum disorder. Thus, it may provide a potentially beneficial therapeutic strategy for managing autism spectrum disorder. Agomelatine may also potentially help reduce sleep disturbances in ASD models.

Agomelatine and Neurogenesis

Neurogenesis is the process by which new nerve cells are formed in the brain. Research has shown that neurogenesis preserves cognitive functioning. It also plays a vital role in neural plasticity and the repair of damaged brain cells affected by aging and brain disorders.

Data from an animal study provides evidence that Agomelatine may promote adult hippocampal neurogenesis in chronically stressed rats. This is encouraging given that hippocampal neurogenesis has been established in different species.

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