Scientific Reference
Melatonin
Evidence profile: Review literature
Melatonin (N-acetyl-5-methoxytryptamine) is a small indoleamine made from tryptophan, chiefly in the pineal gland; it is not a peptide. It is made from serotonin in two steps, acetylation and then methylation, in the pineal gland and in smaller amounts in the retina, gut and other tissues. Pineal production follows a daily rhythm set by the suprachiasmatic nucleus of the hypothalamus: it rises in darkness and is suppressed by light. Human research is substantial and concentrates on circadian physiology and sleep, alongside a large animal literature that includes seasonal breeding. Work on its chemistry as a free-radical scavenger is mostly in vitro or in animals, often at concentrations well above those found in blood.
Mechanism of Action
Two high-affinity melatonin receptors, MT1 and MT2, have been characterised. Both are G-protein-coupled receptors that couple mainly to Gi, lowering cyclic AMP, and both are expressed in the suprachiasmatic nucleus, where rodent studies have linked MT1 to suppression of neuronal firing and MT2 to shifts in the timing of the circadian clock. They are also found in the retina, blood vessels and several peripheral tissues. A third binding site, once labelled MT3, was later identified as the enzyme quinone reductase 2. Apart from receptor signalling, melatonin and several of its metabolites react directly with reactive oxygen and nitrogen species in chemical systems.
Molecular Information
- Type: Amino acid derivative (non-peptide)
- Molecular weight: 232.28 g/mol
- Molecular formula: C13H16N2O2
- CAS: 73-31-4
Published Research
Melatonin Use in the ICU: A Systematic Review and Meta-Analysis
Tang BHY et al. · Critical care medicine · 2025 · Review
PMID 40662882 — View on PubMedMelatonin as a Novel Drug to Improve Cardiac Function and Quality of Life in Heart Failure Patients: A Systematic Review and Meta-Analysis
Daliri AS et al. · Clinical cardiology · 2025 · Review
PMID 40026259 — View on PubMedInterventions for insomnia in cancer patients and survivors-a comprehensive systematic review and meta-analysis
Nissen ER et al. · JNCI cancer spectrum · 2024 · Review
PMID 38781520 — View on PubMedNeonatal magnesium sulphate for neuroprotection: A systematic review and meta-analysis
Shepherd E et al. · Developmental medicine and child neurology · 2024 · Review
PMID 38468452 — View on PubMedEffect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials
Ziaei S et al. · Journal of ovarian research · 2024 · Review
PMID 38965577 — View on PubMedOptimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis
Cruz-Sanabria F et al. · Journal of pineal research · 2024 · Review
PMID 38888087 — View on PubMed