Evidence map›Paper›PMID 40698692›Full record

ArticleCurrent neuropharmacology2026

Exogenous Melatonin as a Sleep-promoting Agent beyond its Chronobiotic Properties: A Scoping Review of its Effects on Key Sleep-wake Neurotransmitters.

Letizia Biso, Nicola Luigi Bragazzi, Marco Bonaso, Erik Bersanetti, Sergio Garbarino, Marco Scarselli

Abstract readScoping Review
In one paragraph

Article in Current neuropharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Letizia BisoDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Nicola Luigi BragazziDepartment of Clinical Pharmacy, Saarland University, Saarbrücken, Germany.
Marco BonasoDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Erik BersanettiDepartment of Pierpaoli Exelyas Srl, Milan, Italy.
Sergio GarbarinoDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal/Child Sciences (DINOGMI), University of Genoa, Genoa, Italy.
Marco ScarselliDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionExogenous melatonin (exo-MLT) is a sleep-promoting agent that modulates key sleep-wake neurotransmitters.

methodsThis scoping review analyzed 623 studies retrieved from PubMed/MEDLINE and ISI/ Web of Science, applying PRISMA methodology to ensure rigorous inclusion criteria. After screening, 58 original research papers were analyzed for exo-MLT's effects on gamma-aminobutyric acid (GABA), serotonin, dopamine, glutamine, norepinephrine, epinephrine, orexin, acetylcholine, adenosine, glycine, galanin, and histamine.

resultsWe identified 20 studies on the GABAergic system, showing that exo-MLT enhances GABA activity through different mechanisms, promoting non-REM sleep and reducing stress-related hyperarousal. On serotonin, 16 studies revealed limited and variable effects depending on the dose and physiological conditions. Total 13 dopamine studies suggested that exo-MLT does not alter physiological dopamine turnover, restoring dopaminergic balance in pathological states. On the glutamatergic system, seven studies showed a compensatory role of exo-MLT on glutamate excitotoxicity. Six studies on norepinephrine highlighted exo-MLT's ability to regulate sympathetic activity. The orexinergic system was the focus of five studies, indicating exo-MLT's inhibitory action on orexinergic neurons, enhancing sleep quality and consolidation. Five studies investigated exo-MLT on the cholinergic system, revealing an enhancing effect on acetylcholine activity in physiological and pathophysiological conditions. Lastly, four studies exploring adenosine and glycine were inconclusive of the exo-MLT effect, while we could not find any data on histamine and galanin. DISCUSSION: This review underscores exo-MLT's mechanisms beyond circadian regulation, offering therapeutic promise in sleep disorders associated with other neuropsychiatric conditions.

conclusionExo-MLT's interactions provide insights into its safety and non-addictive characteristics, supporting its integration into personalized sleep medicine.

Indexed as

MelatoninNeurotransmitter AgentsSleepWakefulnessAnimalsHumansMelatoninNeurotransmitter AgentsMelatoninsleepsleep disorderssleep medicine.sleep-promoting agentsleep-wake neurotransmitters

Identifiers

PMID40698692
PMCPMC13084770

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.