Drug Database
ME

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

PubMedJournal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine2026-09-19

The role of the transdiagnostic sleep and circadian intervention in adolescent bedtime and sleep quality: a pilot study.

Duraccio Kara M KM, Craig Afton B AB, Kamhout Sarah L H SLH, Wright Isabella D ID et al.

Circadian misalignment is prevalent among adolescents and contributes to sleep deficiency and mental health struggles. There is a need for interventions targeting sleep and circadian difficulties in adolescents. This pilot study examined the effectiveness of a Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TSC) in a community-based adolescent sample with circadian misalignment. We hypothesized that TSC would improve sleep timing and duration, lessen circadian misalignment, improve subjective sleep quality, shorten sleep onset latency, and improve mental health outcomes. Thirty-one adolescents (M age = 15.9 years (SD = 1.3); 45.2% female; 67.7% White) with self-reported circadian misalignment completed the six-week TSC intervention. Using a within-subject design, outcomes were assessed via actigraphy, dim-light melatonin onset (DLMO), Morningness-Evening Questionnaire, Pittsburgh Sleep Quality Index, and Depression Anxiety and Stress Scale-21 Item before and after the intervention. Repeated-measure Generalized Linear Models were conducted to examine differences across outcomes from pre- to post-intervention. TSC was associated with a significant earlier shift in sleep midpoint (~ 30 min; p = .023, g = .591) and weekend sleep onset (p = .003, g = .856), alongside improved subjective sleep quality (p = .021, g = .452). No significant changes were observed in DLMO, circadian misalignment index, total sleep duration, sleep onset latency, chronotype, or any mental health outcomes. TSC demonstrated improvements in behavioral sleep timing and perceived sleep quality in a community-based adolescent sample, even without detectable biological circadian phase shifts. These findings extend prior efficacy research into real-world clinical contexts. Future studies should incorporate control groups, longer follow-up periods, and more diverse samples to clarify TSC's mechanisms and broader effectiveness. Circadian misalignment is prevalent among adolescents and contributes to sleep deficiency and mental health struggles, highlighting a need for effective interventions targeting sleep and circadian difficulties in adolescents. The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TSC) is a promising intervention, but more research is needed to fully understand its effectiveness across multiple contexts. This pilot study investigated the effectiveness of TSC on the sleep, circadian functioning, and mental health of adolescents with circadian misalignment. Our results increase our understanding of the strengths and limitations of TSC, which informs future research and clinical practice.

PMID 42760394
Read full article →
PubMedPlant physiology and biochemistry : PPB2026-09-18

Endogenous melatonin mediated by OsCOMT enhances grain yield, nitrogen use efficiency, and grain quality in rice.

Xue Qiancheng Q, Gharib Ahmed A, Li Yaoqing Y, Chen Rujia R et al.

Excessive nitrogen (N) application in rice often leads to diminishing yield returns and compromises grain quality, presenting a key challenge for sustainable rice production. Here, we revealed that OsCOMT, a key regulator that modulates endogenous melatonin levels, simultaneously enhances grain yield, nitrogen use efficiency (NUE), and grain quality under varying N conditions. Using two-year field trials conducted under low, normal, and high N conditions, we found that high-melatonin (OsCOMT-OE) plants consistently produced higher grain yield compared to wild type (WT) across all N regimes, whereas low-melatonin (OsCOMT-Cas9) plants showed significant yield reductions. Notably, WT exhibited minimal yield gains under high N relative to normal N, whereas high-melatonin plants sustained a pronounced increase. This yield advantage was underpinned by melatonin-mediated enhancement of N uptake and utilization efficiency. Mechanistically, elevated melatonin promoted N retention in vegetative tissues during grain filling, thereby delaying leaf senescence and extending photosynthetic activity. This N partitioning strategy also limited excessive N transport to grains, thereby lowering grain protein content and chalkiness while improving eating quality. Collectively, our findings establish endogenous melatonin as a key regulator that coordinates high yield, improved NUE, and superior grain quality under high N conditions, and highlight OsCOMT as a promising genetic target for sustainable rice production.

PMID 42759109
Read full article →
PubMedEuropean archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry2026-09-18

The efficacy of transdermal melatonin in dental anxiety in children: a randomised placebo-controlled clinical trial.

Wahba Nour N, Nagi Basma Mahmoud BM, El-Baraky Iman Ali IA, El-Motayam Ahmed Kamal AK

Dental anxiety, a prevalent barrier to optimum dental care, frequently necessitates pharmacological intervention. Melatonin appears to be a safe anxiolytic in medical settings but remains underexplored in paediatric dental anxiety management. Our objective was to evaluate the efficacy of transdermal melatonin patches in managing dental anxiety in children undergoing invasive dental treatment. 52 children aged 5-7 years undergoing dental treatment requiring infiltration local anaesthesia (LA) were randomly assigned to receive either 2 mg transdermal melatonin patches (n = 26) or placebo patches (n = 26), applied to the forearm 30 min before treatment. Outcomes included physiological parameters (heart rate (HR), systolic blood pressure (SPB), diastolic blood pressure (DPB), peripheral oxygen saturation (SpO2)), and dental anxiety by self-reported Facial Image Scale (FIS). All outcomes were recorded at baseline (T1), post-administration (T2), post-LA (T3), and end of treatment (T4). Transdermal melatonin did not significantly affect either the physiological parameters or the FIS compared to placebo at any timepoint. Intragroup analysis revealed that melatonin protected against the rise in HR and DBP associated with LA injection observed in the placebo group following LA injection. ANCOVA indicated a moderate, statistically significant effect of melatonin on HR at T3 independent of baseline HR (effect size = 9%, P = 0.033, power = 58%). Melatonin induced a transient increase in SpO₂ noted post-administration (mean difference 0.96%, P = 0.019). Transdermal melatonin patches provided modest cardioprotective effects against the haemodynamic stress of dental injections during paediatric dental procedures but did not significantly reduce self-reported dental anxiety.

PMID 42758406
Read full article →
PubMedFrontiers in endocrinology2026-09-18

The circadian-melatonin axis in breast cancer metastasis: molecular mechanisms, organ-specific metastatic niches, and therapeutic opportunities.

Wang Ching-Hsiang CH, Chong Kian-Hwee KH, Cheng Ching-Feng CF, Chang Yao-Jen YJ et al.

Breast cancer metastasis remains the leading cause of disease-related mortality despite major advances in systemic therapy. Increasing evidence indicates that the circadian-melatonin axis may influence metastatic progression by coordinating endocrine signaling, metabolism, immune responses, and tumor cell plasticity. In this review, we summarize current epidemiological, mechanistic, and translational evidence linking circadian disruption and melatonin to breast cancer metastasis. We discuss how core circadian clock genes and melatonin signaling may influence epithelial-mesenchymal transition, cancer stemness, circulating tumor cell dissemination, tumor metabolism, and immune remodeling. We further highlight the emerging potential roles of melatonin in shaping adipocyte-tumor crosstalk and organ-specific metastatic niches, including bone, lung, liver, and brain, where tissue-specific interactions may influence metastatic colonization. Finally, we discuss the clinical potential of circadian chronotherapy, adjuvant melatonin, and circadian biomarker-guided precision medicine. Although substantial experimental evidence supports the anti-metastatic properties of the circadian-melatonin axis, clinical translation remains limited by context-dependent biological effects and the lack of chronobiology-informed trials. Future studies integrating circadian biomarkers with optimized treatment timing and modern systemic therapies may facilitate precision strategies for preventing and treating metastatic breast cancer.

PMID 42755785
Read full article →
PubMedJournal of pineal research2026-09-18

Multi-Omics Analysis Provides Insights Into the Molecular Mechanism of Melatonin-Mediated Cadmium Tolerance in Populus tomentosa.

Sun Li L, An Jiaqi J, Yan Tengyue T, Wang Tao T et al.

Cadmium (Cd) contamination, a major constraint on plant growth, causes a serious threat to ecological safety. Populus tomentosa is a promising woody species for Cd phytoremediation, but the mechanism of Cd phytoremediation by melatonin (MT) in this species remains unclear. To elucidate how MT confers Cd tolerance in P. tomentosa, four treatments (control, MT: 100 μmol·L-1 melatonin, Cd: 100 μmol·L-1 CdCl2, and MT + Cd, CM: 100 μmol·L-1 CdCl2 + 100 μmol·L-1 melatonin) on seedlings were conducted, and integrated analyses of physiological traits, noninvasive micro-test (NMT) data, transcriptomes, and metabolomes were further performed. Cd stress significantly inhibited seedling growth, reduced chlorophyll content, promoted excessive Cd accumulation, and triggered a burst of reactive oxygen species (ROS). Exogenous MT application reversed Cd-induced growth suppression by promoting root Cd2+ efflux while reducing Cd influx, decreasing Cd deposition in leaves, and activating superoxide dismutase and peroxidase to scavenge ROS under Cd treatment. Transcriptomic and metabolomic profiling suggested that metabolic pathways, including hormone signaling, glutathione metabolism, and phenylpropanoid biosynthesis, might be participated in the MT-mediated Cd response. Furthermore, three transcription factors, ERF098, bHLH041, and MYB308, were also identified as candidate regulators of MT-mediated Cd detoxification. Heterologous expression in yeast revealed that MYB308 not only enhanced Cd tolerance but also reduced Cd accumulation under Cd stress. These findings elucidate the multilayered regulatory network underlying MT-enhanced Cd tolerance in P. tomentosa, and provide genetic resources for breeding Cd-resistant tree varieties and theoretical guidance for remediating Cd-contaminated soils.

PMID 42757561
Read full article →
PubMedFrontiers in pharmacology2026-09-18

Pharmacological strategies for intestinal ischemia-reperfusion injury: mechanisms and therapeutic advances.

Wang Wenhui W, Ma Jingran J, Wen Yiru Y, Liu Jieting J

Intestinal ischemia-reperfusion injury is a life-threatening complication of mesenteric ischemia, shock, major surgery, and transplantation. Reperfusion triggers oxidative stress, inflammation, barrier failure, microcirculatory dysfunction, and regulated cell death, leading to mucosal and remote-organ injury. This narrative review summarizes pharmacological strategies targeting oxidative injury, excessive inflammation, dysregulated cell death, and drug delivery, while considering experimental models, administration protocols, and translational feasibility. Thiol compounds, polyphenols, melatonin, SIRT-axis modulators, anti-inflammatory agents, ferroptosis and autophagy modulators, and targeted delivery platforms show therapeutic potential; however, most evidence derives from heterogeneous animal models using prophylactic or peri-reperfusion dosing, and clinical evidence remains very limited. Future studies should use clinically realistic treatment windows, standardized models and outcomes, and rational multimodal regimens.

PMID 42755826
Read full article →

+9996 more articles available with a free account

Sign up free to view all articles →

Ask about melatonin