agomelatine / Generic mfg. - LARVOL DELTA

Agomelatine Alleviates Depressive-Like Behaviors in Mice by Promoting Mitophagy in Parvalbumin-Expressing Neurons of the Hippocampal Ventral Dentate Gyrus. (PubMed, Neuropharmacology) - "In conclusion, agomelatine alleviates CUMS-induced depressive-like behaviors in mice, which is associated with the promotion of mitophagy in vDG PV neurons of the hippocampus, mitigating mitochondrial damage and neuroinflammation. This uncovers a novel mechanism for its efficacy and highlights targeted mitophagy activation as a promising MDD therapeutic strategy."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Metabolic Disorders • Mood Disorders • Psychiatry • ATG5 • BECN1 • MB

Effect of Cytochrome P450 2C9 genetic polymorphism on agomelatine metabolism in vitro. (PubMed, PeerJ) - "These results suggest that special attention should be given to subjects carrying poor metabolizers of CYP2C9 alleles when prescribing agomelatine in clinical practice. This study can provide valuable insights for personalized medicine and reduce adverse reactions to some extent."

Journal • Preclinical • CYP2C9

Mechanistic Study of the Antidepressant Agomelatine in Modulating STING Activity During the Pathogenesis of Systemic Lupus Erythematosus (EULAR 2026) - No abstract available

Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • STING

Analysis of Tasimelteon in Pharmaceutical Formulations and Bulk Based on Design-Based Quality Approach by HPLC and Greenness Evaluation of the Method. (PubMed, J Chromatogr Sci) - "The internal standard that was deemed most suitable was agomelatine, at a concentration of 33.0 μg/mL. In addition, the environmental sustainability of the method was proved using different analytical greenness metrics as National Environmental Methods Index, analytical eco-scale, Analytical Greenness Metric and Green Analytical Procedure Index for evaluating its greenness. The applicability of the method was demonstrated in the analysis of Hetlioz® pseudo formulation."

Journal

Agomelatine-Induced Subjective Double Delusion in Adolescent Bipolar Disorder. (PubMed, Psychopharmacol Bull) - "Following discontinuation of agomelatine and initiation of olanzapine, significant clinical improvement was observed within three weeks. This case highlights the importance of cautious antidepressant use in adolescents at risk for bipolar disorder. Clinicians should closely monitor for emerging manic or psychotic symptoms and provide timely interventions to prevent serious complications."

Journal • Bipolar Disorder • CNS Disorders • Mood Disorders • Pediatrics • Psychiatry

Circadian Regulation of the Endogenous Brain Clearance System Promotes Hematoma Resolution after Intracerebral Hemorrhage in Mice (AAN 2026) - "Disruption of circadian rhythm may therefore impair hematoma clearance.Design/ Male mice underwent collagenase-induced ICH and received circadian disruption (Clock knockout or 48 h sleep deprivation), light intervention (daytime vs. nighttime blue-light exposure), or pharmacological modulation (melatonin + agonist agomelatine vs. receptor antagonist luzindole)... Circadian rhythm promotes hematoma resolution after ICH by upregulating melatonin-dependent AQP4/LRP1/OCLN expression and enhancing glymphatic and vascular clearance pathways. Strengthening circadian rhythm or melatonin signaling may represent a novel therapeutic strategy for improving outcomes after hemorrhagic stroke."

Preclinical • Cardiovascular • Cerebral Hemorrhage • Dyslipidemia • Hematological Disorders • AQP4 • LDLR • LRP1 • OCLN

Clinical trial to evaluate the effectiveness and efficiency of a pre-emptive pharmacogenetic strategy for antidepressant selection in patients with depressive disorder: The PREDICT clinical trial. (clinicaltrialsregister.eu) - P4 | N=240 | Not yet recruiting | Sponsor: Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Biomarker • New P4 trial • CNS Disorders • Depression • Mood Disorders • Psychiatry • HTR2A • SLC6A4

Agomelatine and the potential inverse risk of metabolic disorders: a nationwide cohort study with an active comparator design in Taiwan. (PubMed, Diabetol Metab Syndr) - No abstract available

Journal • Cardiovascular • CNS Disorders • Depression • Diabetes • Hypertension • Metabolic Disorders • Mood Disorders • Psychiatry

The Neuroprotective Effects of Agomelatine in a 3‑Nitropropionic Acid-Induced Rat Model of Huntington's Disease via Brain-Derived Neurotrophic Factor (BDNF)/tropomyosin-Related Kinase Receptor Type B (TrKB)/Phosphoinositide 3‑Kinase (PI3K)/Protein Kinase B (AKT) Activation and Rho-Associated Protein Kinase 1 (ROCK1) Pathway Inhibition. (PubMed, ACS Pharmacol Transl Sci) - "Furthermore, agomelatine administration reduced the expression of ROCK1, suppressing the release of inflammatory responses. Finally, agomelatine possessed neuroprotective activity, as proved by enhancing motor activity and histopathological abnormalities via improving the BDNF/TrKB/PI3K/AKT survival cascade and suppressing the ROCK1 inflammatory pathway."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Huntington's Disease • Inflammation • Movement Disorders • Psychiatry • BDNF • NTRK2 • ROCK1

Management of insomnia symptoms in depressed patients treated with agomelatine, mirtazapine and trazodone: A systematic review and meta-analysis. (PubMed, J Affect Disord) - "All three medications significantly enhance subjective sleep perception and alleviate depressive symptoms. However, agomelatine may lack a definitive effect on improving objective sleep parameters in depressed patients. Future studies should involve larger, high-quality trials with unified methodologies to strengthen the reliability of conclusions."

Journal • Retrospective data • Review • Anesthesia • CNS Disorders • Depression • Insomnia • Mood Disorders • Pain • Psychiatry • Sleep Disorder

Agomelatine Alleviates Methotrexate-Induced Lung Injury by Concurrently Inhibiting CD45/CD68-Positive Immune Cell Infiltration and Modulating the BAX/BCL2 Apoptosis Pathway. (PubMed, J Appl Toxicol) - "These findings provide integrated immunohistochemical and molecular evidence supporting the concurrent modulation of immune cell infiltration and apoptotic signaling by AGO in MTX-induced lung injury. Given its established clinical use and favorable safety profile, AGO may represent a potential adjunctive candidate to reduce the risk of MTX-related pulmonary complications, through concurrent targeting of immune and apoptotic pathways."

Journal • Inflammation • Respiratory Diseases • BAX • BCL2 • CD68 • PTPRC

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