Melatonin for the Treatment of Sleep Disturbances in Major Depressive Disorder

Dolberg, Ornah T.; Hirschmann, Shmuel; Grunhaus, Leon

doi:10.1176/ajp.155.8.1119

Cited by 147 publications

(78 citation statements)

References 10 publications

(4 reference statements)

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“…This is in line with clinical studies showing that melatonin by itself does not have any antidepressant effect in patients suffering from major depressive disorder (MDD; Dalton et al, 2000;Dolberg et al, 1998). In contrast, the efficacy of agomelatine in MDD has been demonstrated in clinical trials vs placebo (Kennedy and Emsley, 2006) and using active comparators such as venlafaxine (Lemoine et al, 2007), sertraline (Kasper et al, 2010), and fluoxetine (Hale et al, 2010).…”

Section: Introductionsupporting

confidence: 72%

Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine, Norepinephrine, and Serotonin Systems in the Rat Brain

Chenu

Mansari

Blier

2012

Neuropsychopharmacol

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Agomelatine is a melatonergic MT1/MT2 agonist and a serotonin (5-HT) 5-HT 2C antagonist. The effects of 2-day and 14-day administration of agomelatine were investigated on the activity of ventral tegmental area (VTA) dopamine (DA), locus coeruleus (LC) norepinephrine (NE), and dorsal raphe nucleus (DRN) 5-HT neurons using in vivo electrophysiology in rats. The 5-HT 1A transmission was assessed at hippocampus CA3 pyramidal neurons. After a 2-day regimen of agomelatine (40 mg/kg/day, i.p.), an increase in the number of spontaneously active VTA-DA neurons (po0.001) and in the firing rate of LC-NE neurons (po0.001) was observed. After 14 days, the administration of agomelatine induced an increase in: (1) the number of spontaneously active DA neurons (po0.05), (2) the bursting activity of DA neurons (bursts/min, po0.01 and percentage of spikes occurring in bursts, po0.05), (3) the firing rate of DRN-5-HT neurons (po0.05), and (4) the tonic activation of postsynaptic 5-HT 1A receptors located in the hippocampus. The increase in 5-HT firing rate was D2 dependent, as it was antagonized by the D2 receptor antagonist paliperidone. The enhancement of NE firing was restored by the 5-HT 2A receptor antagonist MDL-100,907 after the 14-day regimen. All the effects of agomelatine were antagonized by a single administration of the melatonergic antagonist S22153 (except for the increase in the percentage of spikes occurring in burst for DA neurons). The present results suggest that (1) agomelatine exerts direct (2 days) and indirect (14 days) modulations of monoaminergic neuronal activity and (2) the melatonergic agonistic activity of agomelatine contributes to the enhancement of DA and 5-HT neurotransmission.

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Section: Introductionsupporting

confidence: 72%

Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine, Norepinephrine, and Serotonin Systems in the Rat Brain

Chenu

Mansari

Blier

2012

Neuropsychopharmacol

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“…Melatonin treatment has been found effective to treat circadian rhythm disorders [180,190]. As far as its antidepressant activity, melatonin (10 mg/day) was inactive to affect bipolar affective disorder [191] and improved sleep with no effect on symptoms of depression in major depressive disorder [192,193]. Among the analogs developed to improve the efficacy of melatonin's effects, agomelatine (Valdoxan®, Servier, France) has been licensed by the EMEA for the treatment of major depression disorder in adults.…”

Section: Levels Of Amt6s In 12-h Overnight Urine Samplesmentioning

confidence: 99%

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Cardinali¹,

Escames²,

Acuña-Castroviejo³

et al. 2016

J Integr Oncol

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“…Within the central nervous system (CNS), it is involved in several important catabolic pathways including those of serotonin and kynurenine [1,2]. The overview of tryptophan catabolism with relationships with CNS diseases [3][4][5][6][7][8][9][10][11] is illustrated in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders

et al. 2016

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Abnormal levels of kynurenic acid (KYNA) in the human brain are believed to be connected to several central nervous system (CNS) diseases, therefore compounds which affect the production of this crucial metabolite are of interest in CNS drug development. The majority of KYNA production is accounted for by kynurenine aminotransferase-2 (KAT-2) in the mammalian brain; hence this enzyme is one of the most interesting targets with which to modulate KYNA levels. Recently developed human KAT-2 inhibitors with high potencies are known to irreversibly bind to the enzyme cofactor, pyridoxal-5 1 -phosphate (PLP), which may lead to severe side effects due to the abundance of PLP-dependent enzymes. In this study, we report a reversible and competitive inhibitor of KAT-2. Its inhibitory activities were examined using HPLC and surface plasmon resonance (SPR) and compare favorably with other recently reported KAT-2 inhibitors. Our inhibitor, NS-1502, demonstrates suitable inhibitory activity, almost 10 times more potent than the known reversible KAT-2, (S)-ESBA.

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Melatonin for the Treatment of Sleep Disturbances in Major Depressive Disorder

Cited by 147 publications

References 10 publications

Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine, Norepinephrine, and Serotonin Systems in the Rat Brain

Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine, Norepinephrine, and Serotonin Systems in the Rat Brain

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders

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