Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade

  title={Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade},
  author={Mark J. Millan and Mauricette Brocco and Alain P. Gobert and Anne Dekeyne},
RationaleThe novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors and as an antagonist at serotonin (5-HT)2C receptors.ObjectivesTo determine whether, by virtue of its antagonist properties at 5-HT2C receptors, agomelatine elicits anxiolytic properties in rats.MethodsEmploying a combined neurochemical and behavioural approach, actions of agomelatine were compared to those of melatonin, the selective 5-HT2C receptor antagonist, SB243,213, and the benzodiazepine… 

The melatonergic agonist and clinically active antidepressant, agomelatine, is a neutral antagonist at 5-HT(2C) receptors.

Agomelatine behaves as a neutral antagonist at constitutively active h5-HT 2C(INI)Rs and native, cortical 5-HT2CRs and is of interest to determine whether the neutral antagonist properties of agomel atine are related to its favourable clinical profile of antidepressant properties with few side-effects and no discontinuation syndrome.

Beyond the monoaminergic hypothesis: Agomelatine, a new antidepressant with an innovative mechanism of action

  • S. KasperM. Hamon
  • Psychology, Biology
    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
  • 2009
Interestingly, agomelatine demonstrated antidepressant efficacy not only in patients with a moderate depressive episode but also in a more severe depressed subpopulation of patients, and the treatment effect increased with the severity of the disease.

S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models

In vitro and in vivo, the novel benzourea derivative, S32006 is a potent 5-HT2C receptor antagonist, and possesses antidepressant and anxiolytic properties in diverse rodent models.

Influence of the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist, agomelatine, on the rat sleep–wake cycle architecture

Agomelatine possesses a distinctive EEG profile compared with melatonin, ramelteon, and S32006, possibly reflecting co-joint agonist and antagonist properties at MT1/MT2 and 5-HT2C receptors, respectively.

Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties

The present review focuses on the pharmacological properties of this novel antidepressant, strikingly different from that of conventional classes of antidepressants, and opens perspectives towards a better understanding of the physiopathological bases underlying depression.

Anxiolytic effects of the melatonin MT2 receptor partial agonist UCM765: Comparison with melatonin and diazepam

Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.

The findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic, and provide the first direct evidence that activation of BLA 5- HT2 CRs accounts for the short-term aversive effect of antidepressants.

Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies.

There is evidence that stimulation of regionally discrete populations of 5-HT2C receptors is effective in certain behavioural models of antidepressant activity, and promotes neurogenesis in the hippocampus, which underpin interest in 5- HT2C receptor blockade as a strategy for treating depressive and anxious states.

17β-Estradiol augments the neuroprotective effect of agomelatine in depressive- and anxiety-like behaviors in ovariectomized rats

The combined treatment of E2 and Ago is evaluated as a treatment of choice for depression, anxiety, and sleep disturbances associated with menopause and augmented the neuroprotective effect of Ago in OVX rats via its anti-inflammatory and neurotrophic effects.



Preclinical evaluation of the reinforcing and discriminative stimulus effects of agomelatine (S-20098), a melatonin agonist

Results suggest that agomelatine would not produce diazepam-like intoxication in humans, nor would it likely be subject to abuse.

The Novel Melatonin Agonist Agomelatine (S20098) Is an Antagonist at 5-Hydroxytryptamine2C Receptors, Blockade of Which Enhances the Activity of Frontocortical Dopaminergic and Adrenergic Pathways

In contrast to melatonin, agomelatine behaves as an antagonist at 5- HT2B and 5-HT2C receptors: blockade of the latter reinforces frontocortical adrenergic and dopaminergic transmission.

SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety

Agomelatine(S 20098) antagonizes the penile erections induced by the stimulation of 5-HT2C receptors in Wistar rats

Data suggested that the reported effects were not due to the stimulation of melatonin receptors and that, contrary to melatonin, agomelatine exerted 5-HT2C receptor antagonist properties in addition to its agonist activity atmelatonin receptors.

Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study

It is demonstrated that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose.