A Systematic, Updated Review on the Antidepressant Agomelatine Focusing on its Melatonergic Modulation

Abstract

Objective:To present an updated, comprehensive review on clinical and pre-clinical studies on agomelatine.Method:A MEDLINE, Psycinfo and Web of Science search (1966-May 2009) was performed using the following keywords: agomelatine, melatonin, S20098, efficacy, safety, adverse effect, pharmacokinetic, pharmacodynamic, major depressive disorder, bipolar disorder, Seasonal Affective Disorder (SAD), Alzheimer, ADHD, Generalized Anxiety Disorder (GAD), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), anxiety disorders and mood disorder.Study collection and data extraction:All articles in English identified by the data sources were evaluated. Randomized, controlled clinical trials involving humans were prioritized in the review. The physiological bases of melatonergic transmission were also examined to deepen the clinical comprehension of agomelatine’ melatonergic modulation.Data synthesis:Agomelatine, a melatonergic analogue drug acting as MT1/MT2 agonist and 5-HT2C antagonist, has been reported to be an effective antidepressant therapy.Conclusions:Although a bias in properly assessing the “sleep core” of depression may still exist with current screening instruments, therefore making difficult to compare agomelatine’ efficacy to other antidepressant ones, comparative studies showed agomelatine to be an intriguing option for depression and, potentially, for other therapeutic targets as well.

The Beneficial Effects of Agomelatine in Experimental Model of Sepsis Related Acute Kidney Injury

“…[8] It is a synthetic drug, an agonist of melatonin receptors (MT1 and MT2) and an antagonist of serotonin receptor (5-HT2C). [9][10][11] Oxidative stress, which plays a key role in pathogenesis of sepsis, is a leading cause of organ dysfunction in particular. [12] Melatonin at high doses is known for its strong antioxidant and anti-inflammatory activity.…”

A Comparative Study of Efficacy and Safety of Agomelatine and Escitalopram in Major Depressive Disorder

“…Agomelatine dose dependently inhibits the firing rate of SCN neurons and resynchronize circadian rhythms. The 5-HT 2c antagonism has the ability to promote the dopaminergic firing at the ventral tegmental area, frontal cortex, hypothalamus, hippocampus, medulla, pons and also enhance the norepinephrinergic activity at the locus coeruleus [14,15]. The antidepressant effects of agomelatine are claimed to derive from a synergism between its melatonergic agonist and 5-HT 2C antagonist actions [16].…”

The Effect of Agomelatine on the Nociceptive System

“…route to the control group. Because of a lack of studies on the effects of agomelatine on the nociceptive system in the literature, those doses were chosen having regard to similar studies [26][27][28] …”