agomelatine / Generic mfg. - LARVOL DELTA

Agomelatine drives sex-specific neuroprotection and reduced pathology in rat and human Alzheimer's models. (PubMed, bioRxiv) - "Together, these results identify AGO as a promising non-amyloid therapeutic candidate capable of modulating AD-relevant pathways in rodents and human models. The sex-selective efficacy observed in vivo , combined with conserved transcriptional responses across species, underscores the translational relevance of AGO-driven molecular reprogramming in AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • IGF1

Rectal In Situ Thermosensitive Gel Loaded with Agomelatine-Silver Nanoparticles: Formulation and Characterization. (PubMed, Gels) - "The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine."

Journal

Melatonin and agomelatine alleviate ivermectin-induced mouse spermatogonia apoptosis via suppression of oxidative stress and calcium overload. (PubMed, Front Cell Dev Biol) - "Melatonin and agomelatine protect the male reproductive system from drug-induced toxicity by restoring redox homeostasis and mitochondrial function. These findings provide mechanistic insight into melatonin-based therapeutic strategies and the development of fertility preserving agents targeting mitochondria-mediated cellular injury."

Journal • Preclinical • Metabolic Disorders • BAX • BCL2

Altered electroencephalographic microstate dynamics in major depressive disorder and their modulation by melatonergic treatment. (PubMed, J Psychiatr Res) - "This study demonstrates altered EEG microstate dynamics in patients with MDD and provides insights into the neural mechanisms underlying MDD. Microstate abnormalities may serve as potential clinical biomarkers for MDD."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Antidepressant drugs have pharmacological- and time-dependent effects on reinforcement learning in healthy volunteers: An 8 weeks randomized double-blind placebo-controlled study. (PubMed, medRxiv) - "In this double-blind, placebo-controlled study in healthy controls, we used computational modeling to characterize the cognitive effects of two classes of drugs for depression, escitalopram, a typical SSRI which increases serotonergic transmission, and agomelatine, which activates melatonin receptors and antagonizes 5-HT 2C serotonergic receptors. It reveals that they share common beneficial effect on learning along with pharmacological-specific effects. All observed effects varied highly over time, highlighting the non-linearity of the cognitive impact."

Journal • CNS Disorders • Depression • Psychiatry

Antidepressants and the risk of hyponatremia: A multi-institutional cohort study using observational medical outcomes partnership-Common Data Model. (PubMed, Br J Clin Pharmacol) - "Close monitoring of serum sodium levels is essential for SSRI users, especially those aged ≥60 years."

Journal • Licensing / partnership • Cardiovascular • CNS Disorders • Depression • Heart Failure • Psychiatry

Pharmacological management of agitation in dementia: An evidence-based review with expert consensus. (PubMed, J Chin Med Assoc) - "Among the approved agents, brexpiprazole demonstrated the strongest evidence and most favorable safety profile. Risperidone and aripiprazole are effective, but require careful monitoring for cerebrovascular and extrapyramidal risks. Selected antidepressants, particularly citalopram and agomelatine, should be considered when safety is prioritized. Anticonvulsants, acetylcholinesterase inhibitors, and memantine have limited efficacy and should be reserved for refractory cases. Long-term or routine pharmacological use is not supported by current evidence. Future research should focus on identifying responsive patient subgroups, optimizing dosing strategies, and integrating medications into individualized, multidisciplinary care plans."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Agomelatine 3D-printed microneedles as a potential drug delivery system for the treatment of depression. (PubMed, Int J Pharm) - "Mechanical testing showed that Pyramid and Cone geometries were the most promising in puncture tests, and stability testing revealed the need for light- and moisture-resistant packaging. The formulations selected based on the obtained results will be further investigated on the way to create a transdermal alternative to agomelatine oral tablets and increase the effectiveness of depression treatment."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Can We Develop Glioma Subtype-Specific Precision Medicines? An Integrative Machine Learning Pipeline for Biomarker Discovery and Drug Repurposing for Glioblastoma and Low-Grade Glioma. (PubMed, OMICS) - "Repurposed drug candidates were then predicted via signature-based prioritization and evaluated using molecular docking simulations, revealing six promising compounds for GBM (vandetanib, capecitabine, melatonin, agomelatine, ramelteon, and tasimelteon) and one for LGG (ambroxol). This study demonstrates the utility of combining class-balancing, feature selection, and drug repurposing pipelines to uncover clinically relevant glioma biomarkers and therapeutic candidates, thus providing a computational foundation for future experimental and translational validation in these brain cancers and neuro-oncology."

Biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ANK3

STAT3 Signaling Mediates Agomelatine Restoration of Prefrontal Cortex Synaptic Plasticity in Chronic Social Defeat Stress Mice. (PubMed, Mol Neurobiol) - "We further applied AG490, an inhibitor of STAT3, to demonstrate that the therapeutic mechanism of agomelatine improves synaptic plasticity through STAT3-regulated phosphorylation of GSK3β. Taken together, these results demonstrated that STAT3-regulated downstream molecules are potential therapeutic targets for the rapid action of antidepressants."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • STAT3

Parietal alpha asymmetry as a diagnostic marker for depression and a predictive biomarker for anhedonia improvement after melatonergic antidepressant treatment. (PubMed, J Affect Disord) - "PAA, particularly at P7-P8, demonstrated diagnostic utility, while P3-P4 asymmetry was associated with treatment-related improvement in anhedonia. This study extends prior work by including a larger unmedicated MDD cohort, focusing on melatonergic treatment, and employing subitem-level anhedonia measures. Findings support PAA as a state-sensitive biomarker for diagnostic classification and prognosis in MDD, warranting replication and mechanistic investigation."

Biomarker • Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Protective role of agomelatine via modulation of TLR4/NF-κB: NLRP3/IL-1β signaling pathways in testosterone-induced benign prostatic hyperplasia in rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The findings from this study provide new evidence that AGO can alleviate testosterone-induced BPH in rats, likely through the inhibition of the TLR4/NFκB and NLRP3/IL-1β signaling pathways. These results suggest that AGO could be a promising therapeutic option for managing BPH."

IO biomarker • Journal • Preclinical • Benign Prostatic Hyperplasia • IL1B • MYD88 • NLRP3 • TLR4

Reflections on a Study of Low-Dose Agomelatine as Add-on for Agitation in Alzheimer's Disease. (PubMed, Am J Geriatr Psychiatry) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Investigating the Role of GABAergic Interneurons in the Antidepressant-like Mechanism of Agomelatine. (PubMed, Neurochem Int) - "The antidepressant effects of AGO involve the modulation of GABAergic neural circuits as a critical but non-exclusive target, alongside the restoration of GABAergic-glutamatergic balance, synaptic function, and clock gene expressions. These findings highlight AGO's potential in normalizing disrupted neuronal function in depression and offer insights into novel multi-target therapeutic strategies."

Journal • CNS Disorders • Depression • Mental Retardation • Psychiatry • CLOCK • SLC2A1

A Novel Zeolite-Carbon Nanotube Composite Electrode for the Electrochemical Analysis of Agomelatine in Real Samples. (PubMed, Nanomaterials (Basel)) - "Differential pulse voltammetry (DPV) was utilized for the quantitative determination of AGO, with optimization performed on instrumental parameters, supporting electrolyte pH, and preconcentration time (tacc). Using the Britton-Robinson buffer (BRB) solution at pH 3.0, the Cu-ZY/MWCNTs-GCE exhibited a linear response to AGO concentrations ranging from 8.2 × 10-9-9.6 × 10-7 mol L-1 (0.002-0.23 mg L-1), achieving a detection limit (LOD) of 4.3 × 10-9 mol L-1 (1.04 µg L-1) with a preconcentration time of 60 s. The successful determination of AGO in pharmaceutical formulations, wastewater, and biological fluids, with recoveries ranging from 98.0 to 113.0%, demonstrates the effectiveness and practical applicability of the Cu-ZY/MWCNT-GCE-based voltammetric method for agomelatine analysis in complex matrices."

Journal

Agomelatine alleviates hypoxia-induced pulmonary arterial hypertension by activating mitophagy via the SIRT1/FoxO1/ULK1 signaling pathway. (PubMed, Biochem Pharmacol) - "The present investigation was designed to evaluate the ameliorative potential of AGM on pulmonary vascular remodeling in a SU5416/hypoxia (SuHx)-induced PAH rat model, and to elucidate the concomitant mechanistic pathways. In contrast, inhibition of SIRT1 resulted in increased FoxO1 acetylation, which subsequently downregulated ULK1 expression and impaired mitophagy. Collectively, these findings establish that AGM exerts therapeutic effects in PAH by enhancing ULK1-dependent mitophagy through modulation of the SIRT1/FoxO1 signaling axis, underscoring its potential as a novel therapeutic candidate for PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Effects and Mechanisms of Melatonin Receptor Agonist and Antagonist on Disease Progression in a 6-OHDA-Induced Parkinson's Disease Rat Model. (PubMed, J Integr Neurosci) - "Both AG and LU demonstrated neuroprotective potential in 6-OHDA-induced PD rats. AG may exert its effects by enhancing endogenous MLT signaling, while LU may protect neurons by modulating excessive MLT activity. These findings highlight the complex regulatory role of the MLT pathway in PD progression and suggest stage-dependent therapeutic benefits of MLT receptor modulators."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Agomelatine normalizes region-specific, diurnal mGluR5 dysregulation in a chronic mild stress rat model of depression. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "These findings reveal significant region-specific and diurnal alterations in mGluR5, emphasizing the role of time-of-day dependent timing in regulating mGluR5 and its association with depressive-like behaviors. Furthermore, the selective normalization of mGluR5 by agomelatine in responders reinforces its potential as a targeted therapeutic approach for MDD."

Journal • Preclinical • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Serotonin receptor 4 in the ventral CA3 regulates agomelatine-induced anxiolytic-like behaviors. (PubMed, Acta Pharmacol Sin) - "Together, these results suggest that agomelatine's anxiolytic effects are closely associated with the suppression of 5-HTR4 expression in the vCA3, along with modulation of neuronal activity and GPCR signaling. This study not only uncovers the molecular mechanisms underlying agomelatine's anxiolytic mechanism but also identifies 5-HTR4 as a potential target for anxiety disorders."

Journal • CNS Disorders • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder • CA3 • FOS

Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis. (PubMed, Transl Psychiatry) - "Commonly used antidepressants have different gastrointestinal effects. Duloxetine, levomilnacipran, and vilazodone carry a higher risk of inducing nausea and vomiting, whereas trazodone, amitriptyline, agomelatine, and mirtazapine tend to be better tolerated. Amitriptyline, clomipramine, and reboxetine are more prone to induce constipation. Diarrhoea is more commonly associated with vilazodone, fluvoxamine, and sertraline. Amitriptyline, reboxetine, and duloxetine are more likely to cause anorexia. Amitriptyline, reboxetine, and trazodone are related to causing dry mouth. Compared with the placebo, amitriptyline, fluoxetine, and paroxetine were associated with a greater incidence of dyspepsia."

Journal • Retrospective data • Review • Anorexia • CNS Disorders • Constipation • Depression • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry • Xerostomia

Agomelatine Targets Aquaporin-4 Polarization to Rescue Glymphatic Dysfunction in Parkinson's Disease. (PubMed, Neurosci Bull) - "Our findings establish AGM as the first melatoninergic agent targeting the glymphatic-AQP4 axis in PD, shifting therapeutic strategies from symptomatic relief to disease modification. This provides clinical rationale for repurposing circadian regulators to decelerate PD progression through enhanced protein clearance."

Journal • CNS Disorders • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • ARNTL • BMAL1

Excessive Yawning Induced by Duloxetine in a Patient With Depression With Successful Agomelatine Substitution: A Case Report. (PubMed, Am J Ther) - No abstract available

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Part A Phase I, Single Ascending Dose Trial of Agomelatine in Healthy Participants (ANZCTR) - P1 | N=15 | Recruiting | Sponsor: Seaport Therapeutics Australia Pty LTD | Not yet recruiting ➔ Recruiting | N=10 ➔ 15

Enrollment change • Enrollment open • Trial initiation date • Mood Disorders • Psychiatry

Effects of Agomelatine on Sleep Across Populations: A Systematic Review and Meta-Analysis. (PubMed, J Sleep Res) - "Agomelatine was found to cause marginally more adverse effects than placebo (RR = 1.05, 95% CI: 1.00; 1.11). Overall, agomelatine appears to slightly improve sleep quality and is well-tolerated and safe, although the limited data for many outcomes warrant cautious interpretation."

Journal • Retrospective data • Review • CNS Disorders • Insomnia • Sleep Disorder

Evaluating the Quality of Evidence for Pharmacological Treatment of Depressive Disorders (AACAP 2025) - "SSRIs (GRADES 1A-2C) and SNRIs (1B) are effective in the treatment of pediatric MDD. Tricyclic antidepressants (2B) and monoamine oxidase inhibitors (2C) have failed to consistently demonstrate efficacy, and they have unfavorable risk-to-benefit profiles. Esketamine, agomelatine, bupropion, transcranial magnetic stimulation, and other emerging classes of treatment may be safe and effective but merit further testing.ADP, DDD, NM"

CNS Disorders • Depression • Mood Disorders • Pediatrics • Psychiatry