Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration

Molteni, Raffaella; Calabrese, Francesca; Pisoni, Serena; Gabriel, C.; Mocaër, Elisabeth; Racagni, Giorgio; Riva, Marco A.

doi:10.3109/15622970903447659

Cited by 61 publications

(45 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have recently demonstrated that an acute injection of agomelatine can up-regulate the expression of BDNF messenger RNA (mRNA) levels in the prefrontal cortex through the functional interaction between melatonergic MT 1 /MT 2 and serotonergic 5-HT 2C receptors (Molteni et al 2010), thus preventing the circadian down-regulation of the neurotrophin.…”

Section: Introductionmentioning

confidence: 99%

Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…7 Similarly, agomelatine produces an increase in gene expression of brain-derived neurotrophic factor (BDNF) in prefrontal cortex that is not reproduced with melatonin or 5-HT 2C antagonism alone. 8 Brain-derived neurotrophic factor has been implicated in depression and the response to antidepressant therapy. 9 However, the affinity of agomelatine for 5-HT 2C receptors is significantly lower than its ability to bind melatonin receptors.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Drug information update: agomelatine

Whiting

Cowen

2013

Psychiatrist

View full text Add to dashboard Cite

The melatonin analogue, agomelatine, is the first antidepressant approved by the European Medicines Agency which is not monoaminergic. Agomelatine is proposed to act as an agonist at melatonin (MT1 and MT2) receptors, and an antagonist at 5-HT 2C receptors. Controlled studies have suggested favourable efficacy and tolerability profiles; however, agomelatine is not without its controversies, with recent meta-analyses showing only marginal advantages over placebo. It is nevertheless an intriguing agent pharmacologically and here we provide a synopsis of its proposed mechanisms of action, indications and side-effects in the treatment of unipolar major depression. Mechanism of actionDisturbances of the sleep-wake cycle and diurnal variation in mood are common symptoms of depression. A role for abnormalities in circadian rhythm in the pathophysiology of depression therefore makes intuitive sense, and has long been explored in treatments such as sleep deprivation and light therapy.1 However, it is not yet clearly established whether there is a consistent circadian 'phase-shift' in patients with major depression or (as seems more likely in this heterogeneous disorder) that some, but not all, patients have variable kinds of circadian disturbances. For example, the pineal hormone melatonin is a reliable marker of circadian rhythm and the activity of the circadian 'oscillator' in the suprachiasmatic nucleus (SCN). However, despite many studies it is still not clear whether there are abnormalities in the amplitude and timing of melatonin secretion in patients with depression.2 Nevertheless, it is known that in both animals and humans appropriately timed administration of melatonin has the capacity to shift circadian rhythms, and melatonin is used for this purpose, for example, in delayed sleep-phase syndrome.3 Agomelatine (N-[2-(7-methoxy-1-napthyl)ethyl]acetamide) is a melatonin analogue, binding with high affinity to MT1 and MT2 G-protein coupled receptors. 4 Melatonin receptors are expressed in numerous regulatory areas of the brain, including the SCN.5 MT1 activation regulates amplitude of circadian rhythmicity via inhibition of SCN neurons, and MT2 activation is involved in phase-shifts and entrainment of the rhythm.6 Additionally, and distinctly from melatonin, agomelatine is a competitive antagonist at 5-HT 2C and 5-HT 2B receptors, and in animal studies, 5-HT 2C antagonism has the ability to increase noradrenaline and dopamine release in the prefrontal cortex. 4 The antidepressant effects of agomelatine are claimed to derive from a synergism between its melatonergic and 5-HT 2C actions. Thus results from animal experimental studies of behavioural models of depression show that melatonin or 5-HT 2C antagonists alone are insufficient to produce the full antidepressant activity of agomelatine. Similarly, agomelatine produces an increase in gene expression of brain-derived neurotrophic factor (BDNF) in prefrontal cortex that is not reproduced with melatonin or 5-HT 2C antagonism alone. 8 Brain-derived neurotrophic fact...

show abstract

“…Its mode of action may be explained by the synergy of MT 1 /MT 2 and 5-HT 2C receptors, which increases noradrenergic and dopaminergic neurotransmission, and a specific release of noradrenaline and dopamine has been described in the prefrontal cortex without effect on the extracellular levels of serotonin [3][4][5]. In addition, an increase of neurotrophic factors (e.g., brain-derived neurotrophic factor, BDNF) and a decrease in stress-related glutamate elevation have also been described [2,6,7] as well as resynchronization of circadian rhythms [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Pooled Analysis of Four Non-Interventional Studies: Effectiveness and Tolerability of the Antidepressant Agomelatine in Daily Practice

Laux

Barthel

Hajak³

et al. 2017

Adv Ther

View full text Add to dashboard Cite

Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration

Cited by 61 publications

References 30 publications

Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine

Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine

Drug information update: agomelatine

Pooled Analysis of Four Non-Interventional Studies: Effectiveness and Tolerability of the Antidepressant Agomelatine in Daily Practice

Contact Info

Product

Resources

About