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melatonin

✓ Approved

Clinigen Group · MTNR1A · Small Molecule

What is melatonin?

melatonin is a small molecule developed by Clinigen Group. It is approved for therapeutic indications via oral (po).

Drug Profile

CompanyClinigen Group
Drug ClassSmall Molecule
Molecular TargetMTNR1A, MTNR1B
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Clinigen Group

Mechanism of Action

Molecular Targets

melatonin acts on 2 molecular targets:

MTNR1Amelatonin receptor 1A (MEL-1A-R, MT1)
MTNR1Bmelatonin receptor 1B (FGQTL2, MT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

melatonin is developed for 2 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersInsomnia✓ Approved
Psychiatric disordersSleep disorder✓ Approved

Related Research Articles

PubMedFrontiers in immunology2026-10-07

Melatonin is associated with cell-type-specific inflammatory and oxidative stress responses at the maternal-fetal interface.

Joseph Tyana T TT, Adekambi Toidi T, Brewer Kyra K, Schuch Viviane V et al.

Melatonin regulates inflammation and oxidative stress at the placenta, but its effects on specific placental cell types remain unclear. This study investigated how melatonin influences inflammatory and oxidative stress responses, cytokine secretion, NRF2-associated antioxidant responses, and transcriptomic responses in JEG-3 trophoblast-like cells and primary decidual macrophages exposed to lipopolysaccharide (LPS). Melatonin reduced LPS-induced inflammatory cytokine production and intracellular reactive oxygen species accumulation, with pretreatment producing the strongest anti-inflammatory effects. Although NLRP3 transcript expression differed according to treatment sequence, melatonin was associated with reduced inflammatory cytokine secretion despite limited changes in total NLRP3 protein expression. Melatonin also differentially influenced antioxidant responses across placental cell types, with decidual macrophages exhibiting broader functional and transcriptional changes than JEG-3 trophoblast-like cells. Transcriptomic profiling revealed dose- and cell type-dependent effects, with decidual macrophages exhibiting altered expression of genes and pathways associated with inflammatory signaling, oxidative phosphorylation, and reactive oxygen species regulation. In contrast, JEG-3 trophoblast-like cells demonstrated limited transcriptional remodeling and more modest engagement of inflammatory signaling pathways than primary decidual macrophages. These findings suggest that melatonin differentially modulates inflammatory and oxidative stress responses across placental cell types at the maternal-fetal interface. Collectively, these data support the potential role of melatonin in promoting placental redox-inflammatory balance during inflammatory stress and provide a foundation for future studies in physiologically relevant models.

PMID 42841030
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PubMedFrontiers in physiology2026-10-07

Amine-responsive Rhodopsin-like GPCRs in ocular pathology: mechanistic associations, candidate biomarkers, and therapeutic potential.

Yu Han H, Li Jia J, Song Jike J, Bi Hongsheng H

Rhodopsin-like G protein-coupled receptors (GPCRs) play a pivotal role in ophthalmic pathologies, and recent studies have substantially advanced our understanding of their underlying molecular mechanisms. Amine-responsive Rhodopsin-like GPCRs (ARh-GPCRs), encompassing adrenoceptors, dopamine receptors, muscarinic acetylcholine receptors, histamine receptors, serotonin receptors, melatonin receptors, and trace amine-associated receptors, are involved in a variety of ocular pathological processes and have emerged as key therapeutic targets. Elucidating their functional roles, alongside those of their ligands and downstream signaling macromolecules, holds considerable potential for the development of candidate biomarkers for early diagnosis, disease classification, prognostication, and predicting treatment response in specific ocular disorders. Despite significant progress, a comprehensive integration of their dual candidate biomarker-therapeutic roles across diverse ocular disorders remains largely unexplored. This narrative review summarizes and critically integrates current evidence on the regulatory roles and therapeutic potential of these receptors in ocular pathologies, with particular attention to their mechanistic involvement, candidate biomarker potential, and therapeutic relevance. Furthermore, we summarize the current research limitations and propose future directions to enhance the understanding of their molecular mechanisms, ultimately facilitating the development of precise diagnostic and therapeutic strategies.

PMID 42840672
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PubMedFrontiers in immunology2026-10-06

Melatonin attenuates inflammation, remodeling, and oxidative stress in experimental models of asthma and COPD.

Ribeiro Cristiane de Cássia CC, João Marcela de Sousa MS, de Almeida Francine Maria FM, Fukuzaki Silvia S et al.

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by persistent airway inflammation, oxidative stress, and structural remodeling, leading to progressive impairment of lung function. Melatonin has anti-inflammatory and antioxidant properties and may represent a promising therapeutic strategy for chronic airway diseases. To evaluate the therapeutic effects of melatonin on airway hyperresponsiveness, inflammation, oxidative stress, and remodeling in experimental models of asthma and COPD. Forty male BALB/c mice were allocated into five groups (n = 8/group): SAL, OVA, OVA+MEL, ELA, and ELA+MEL. Asthma and emphysema were induced by ovalbumin and elastase, respectively. Melatonin (15 mg/kg, intraperitoneally) was administered from days 22 to 27. Respiratory mechanics, bronchoalveolar lavage fluid, immunohistochemistry, and gene expression analyses were performed to evaluate inflammatory cytokines, remodeling markers, and oxidative stress-related proteins. Melatonin significantly attenuated airway hyperresponsiveness in the asthma model, reducing respiratory mechanical parameters, inflammatory cell infiltration, and eosinophilia. In both asthma and emphysema models, melatonin markedly decreased the expression of pro-inflammatory cytokines, remodeling markers (MMP-9, MMP-12, TIMP-1, and TGF-β), and oxidative stress-related mediators (NF-κB and iNOS). These findings were further supported by gene expression analyses, demonstrating broad suppression of inflammatory cytokines following treatment. Melatonin attenuated inflammation, oxidative stress, and airway remodeling while improving lung function, particularly in experimental asthma. These findings highlight melatonin as a promising adjunctive therapeutic strategy for chronic inflammatory lung diseases by simultaneously targeting multiple pathogenic pathways.

PMID 42834959
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PubMedPlant physiology and biochemistry : PPB2026-10-06

Melatonin and hemin co-application reprograms lipolysis, oleosin accumulation and H2S metabolism in NaCl-stressed sunflower seedlings.

Basak Ganapati G, Barman Chandan C, Panda Bikash Kumar BK, Gupta Ravi R et al.

Salt stress adversely affects seed germination and lipid mobilization in germinating sunflower seedlings. Notably, recovery in the rate of lipolysis is crucial to promote stress tolerance, thereby imparting longevity to the seedlings. Melatonin has been previously reported to regulate lipolysis in NaCl-stressed sunflower seedling cotyledons. While hemin (oxidized form of heme) is known to function as a metabolic regulator in plants, no substantial reports are available to understand the combined impact of melatonin and hemin application in the regulation of lipid mobilization during seed germination. The present work hypothesizes that melatonin and hemin co-application escalates lipolysis thereby accompanying changes in proteolytic activity and H2S metabolism in NaCl-stressed sunflower seedling cotyledons. Seedlings exhibited reduced activity of lipolytic enzymes (fatty acyl-ester hydrolase, lipoxygenase, and phospholipase) accompanying a slower oil body mobilization under salinity stress. However, co-application of melatonin and hemin significantly reversed these effects thereby suggesting a faster rate of oil body degradation and lipid mobilization. Electrophoretic analysis of the lipolytic enzymes revealed isoform-specific changes in their expression in different treatment regimes. Confocal laser scanning microscopic analysis and spectrofluorometric estimation revealed intense H2S accumulation under NaCl stress, melatonin and hemin treatment which was correlated with the up-regulation of a 43 kDa L-cysteine desulfhydrase isoform. To sum up, the present work bears agronomic importance for the regulatory role of melatonin and hemin in modulating lipid mobilization and salt-sensitivity of oil seed crops.

PMID 42837981
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PubMedReproductive sciences (Thousand Oaks, Calif.)2026-10-06

Targeting the Nicotine-driven Maladaptive ER Stress Axis: Protective Roles of Melatonin and Coenzyme Q10 in Rat Testis.

Eraslan Sakar Aysel A, Yildiz Cengiz C, Coskun Nurdan N, Sengul Seydi Ahmet SA et al.

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and cellular homeostasis and is highly sensitive to oxidative stress. Nicotine is a potent pro-oxidant; however, its effects on ER stress signaling in testicular tissue and the protective potential of melatonin and coenzyme Q10 (CoQ10) remain insufficiently defined. This study investigated nicotine-induced sperm dysfunction and the involvement of oxidative stress-mediated ER stress pathways in rat testes. Two-month-old male Wistar albino rats (n = 48) were assigned to control, nicotine, nicotine + melatonin, nicotine + CoQ10, nicotine + melatonin + CoQ10, and melatonin + CoQ10 groups. Sperm quality was evaluated, and testicular tissue was analyzed for oxidative stress markers, ER stress-related gene expression, histopathological alterations, and immunohistochemical localization of proteins. Nicotine exposure significantly impaired sperm motility and membrane integrity and increased abnormal morphology, mortality, and apoptosis (p < 0.001). These effects were associated with elevated lipid peroxidation and depletion of antioxidant defenses, including reduced glutathione, glutathione peroxidase, and catalase (p < 0.001). Melatonin and/or CoQ10 partially restored sperm quality and antioxidant capacity. Moreover, antioxidant treatment significantly downregulated ER stress-associated genes (Activating transcription factor 4-ATF4; Activating transcription factor 6-ATF6; C/EBP homologous protein-CHOP; 78 kDa glucose-regulated protein-GRP78; inositol-requiring enzyme 1 alpha-IRE1α; and protein kinase RNA-like endoplasmic reticulum kinase-PERK) and reduced CHOP immunoreactivity, while CoQ10 selectively enhanced XBP-1 immunoreactivity. In conclusion, nicotine-induced testicular dysfunction is mediated by oxidative stress-driven ER stress activation, whereas melatonin and CoQ10 confer protection through modulation of redox balance and ER stress signaling.

PMID 42834319
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PubMedRegenerative biomaterials2026-10-06

Niosome-mediated melatonin delivery via SilMA/GelMA microneedles promotes healing of sleep deprivation-aggravated oral ulcers.

Xie Ying Y, Huang Qi Q, Jiang Xinzhi X, Liu Kehao K et al.

Sleep disturbance disrupts immune homeostasis and impairs oral mucosal healing, yet effective local immunomodulatory strategies remain limited. Here, we identify excessive neutrophil extracellular traps (NETs) as a key mediator linking sleep deprivation to delayed oral wound closure. NETs-associated proteases compromise epithelial barrier function and suppress repair cell migration. To address this, we developed a melatonin-loaded niosome-incorporated silk fibroin methacrylate (SilMA)/gelatin methacryloyl (GelMA) composite hydrogel microneedle (Nio-MT@S-G MN) for localized melatonin delivery and regulation of the NET-associated inflammatory microenvironment. Niosomes achieve efficient encapsulation and sustained melatonin release, while SilMA/GelMA microneedles enable transmucosal administration with favorable mechanical strength. In vitro, Nio-MT@S-G MN promotes keratinocyte migration, reduces NETs marker expression and extracellular DNA release in neutrophils, and alleviates NETs-mediated inhibition of tight junction Zonula occludens-1 (ZO-1) expression. In mice combining sleep deprivation and oral ulcers, local Nio-MT@S-G MN application attenuates NETs deposition and inflammation, restores epithelial barrier proteins and significantly accelerates ulcer closure. By integrating controlled drug delivery with immune microenvironment regulation, this microneedle provides a translational strategy for treating sleep disorder-aggravated mucosal injuries. It may also be applicable to other chronic wounds characterized by dysregulated neutrophil responses.

PMID 42836179
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