Melatonin
| Category | Compounds |
|---|---|
| Also known as | N-Acetyl-5-methoxytryptamine |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | circadianpinealindoleamineantioxidantresearch |
Overview
Melatonin is a small indoleamine hormone synthesized principally by the pineal gland from tryptophan via serotonin intermediates. Its secretion rises at night and falls during the day, making it the primary chemical signal of darkness that synchronizes circadian rhythms with the light-dark cycle. Beyond chronobiology, melatonin has well-documented antioxidant activity and is expressed as a signaling molecule in many non-pineal tissues including the gastrointestinal tract, skin, and immune system.
Clinically, melatonin is used for sleep onset difficulties, jet lag, delayed sleep phase syndrome, and as a circadian regulator in blind individuals with free-running rhythms. Research interest extends to neuroprotection, oncology (notably via modulation of estrogen pathways), and longevity — the latter linking melatonin to pineal bioregulators such as Epitalon and Pinealon.
In peptide research contexts, melatonin is often cross-referenced with DSIP (delta sleep-inducing peptide), Orexin-A, and Klotho as aging- and sleep-related mediators.
Structure / Chemistry
Melatonin is N-acetyl-5-methoxytryptamine (molecular formula C13H16N2O2, MW ~232 g/mol). It is a small, lipophilic molecule that crosses cell membranes and the blood-brain barrier readily.
Mechanism of Action
Melatonin acts through two G-protein-coupled receptors (MT1 and MT2) expressed in the suprachiasmatic nucleus and other brain regions, influencing circadian phase and sleep propensity. It also exerts receptor-independent antioxidant effects through direct free-radical scavenging and induction of endogenous antioxidant systems. Tissue-level actions include modulation of immune signaling and, in the gastrointestinal tract, roles in motility and mucosal protection.
Research Summary
| Area | Finding | Reference |
|---|---|---|
| Sleep onset | Shortened sleep latency in insomnia | Buscemi et al., BMJ 2006 |
| Jet lag | Reduced jet-lag symptoms with timed dosing | Herxheimer & Petrie, Cochrane 2002 |
| Blind | Entrainment in blind individuals | Sack et al., NEJM 2000 |
| Antioxidant | Free-radical scavenging and mitochondrial effects | Reiter et al., J Pineal Res 2016 |
| Cancer | Adjuvant studies in breast/prostate oncology | Srinivasan et al., Integr Cancer Ther 2011 |
Pharmacokinetics
Oral melatonin is absorbed rapidly but undergoes significant first-pass metabolism. Plasma half-life is short (approximately 30-60 minutes), which has motivated sustained-release formulations for sleep maintenance. Research doses range widely, from sub-milligram physiological replacement to several milligrams used in sleep and clinical studies. Specific doses are reference only.
Common Discussion Topics
- Physiological vs. pharmacological dosing for sleep onset.
- Relationship to pineal research peptides Epitalon and Pinealon.
- Antioxidant and immune-modulating effects beyond sleep.
- Evening light exposure and melatonin suppression.
- Regulatory status — OTC in the US, prescription in many other countries.
Related Compounds
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Related entries
- DSIP— A naturally occurring nonapeptide first isolated from rabbit brain in 1977, studied for its role in sleep regulation, stress response modulation, and neuroendocrine function.
- Epithalon— A synthetic tetrapeptide studied for telomerase activation, pineal gland regulation, and lifespan extension in animal models, based on decades of research by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology.
- Klotho— Klotho is an anti-aging protein that functions both as a membrane co-receptor and as a circulating hormone, with roles in phosphate handling, cognition, and longevity.
- Orexin-A— A 33-amino acid excitatory neuropeptide produced by lateral hypothalamic neurons that serves as the primary endogenous regulator of wakefulness and arousal, with loss of orexin-producing neurons being the direct cause of type 1 narcolepsy.
- Pinealon— Pinealon is a Khavinson-class short peptide (Glu-Asp-Arg) associated with pineal and brain bioregulatory research in longevity models.