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Melatonin

Metabolic & Circadian Hormones
N-Acetyl-5-methoxytryptamineCircadin

Overview

Melatonin, also known as N-Acetyl-5-methoxytryptamine or Circadin, is an endogenous hormone primarily produced by the pineal gland in the brain. It belongs to the class of indoleamines and is synthesized from the amino acid tryptophan. Melatonin is also available in synthetic form for research and therapeutic purposes. Researchers have extensively studied melatonin for its role in regulating circadian rhythms and sleep-wake cycles. It is also involved in modulating seasonal biological functions and has been investigated for its antioxidant properties and potential effects on mood disorders. Melatonin acts primarily through melatonin receptors MT1 and MT2, which are G-protein-coupled receptors. Activation of these receptors influences the sleep-wake cycle by modulating the release of neurotransmitters and hormones involved in circadian regulation. Researchers have observed that melatonin's action involves the inhibition of adenylate cyclase and the modulation of intracellular cAMP levels. The pharmacokinetic properties of melatonin include a short circulating half-life of approximately 20 to 50 minutes. It is metabolized primarily in the liver by cytochrome P450 enzymes, particularly CYP1A2. Oral bioavailability is low due to significant first-pass metabolism. Clinically, melatonin is used for the management of sleep disorders, particularly in cases of insomnia and jet lag. In many countries, it is available over-the-counter, while in others, it may require a prescription. Researchers have found it to be generally well-tolerated, with a favorable safety profile. Regulatory standing varies by country, reflecting differences in classification and availability.

Mechanism of Action

Melatonin acts on MT1 and MT2 receptors, which are G-protein-coupled receptors. Activation of these receptors influences circadian rhythms by modulating neurotransmitter release and intracellular signaling pathways, such as the inhibition of adenylate cyclase and reduction of cAMP levels.

Molecular Data

FormulaC13H16N2O2
Molecular Weight232.28 g/mol
CAS Number73-31-4
PubChem CID896

Half-Life & Pharmacokinetics

EndogenousCirculating half-life ~20 to 50 minutes
OralPoor bioavailability due to first-pass metabolism

Oral administration is subject to significant first-pass metabolism, reducing bioavailability.

Storage

Temperature

Store at room temperature (15-30°C)

Light

Protect from light

Form

Stable in solid form for extended periods

Notes

Avoid exposure to moisture and excessive heat.

Solubility

Melatonin is poorly soluble in water but soluble in ethanol and other organic solvents.

Legal Status

🇩🇪DE

In Germany, melatonin is available by prescription (verschreibungspflichtig) for certain formulations.

🇺🇸US

In the USA, melatonin is available over-the-counter as a dietary supplement and is not regulated by the FDA as a drug.

🇦🇺AU

In Australia, melatonin is classified as a Schedule 4 (S4) prescription-only medicine.

🇬🇧UK

In the UK, melatonin is classified as a prescription-only medicine (POM) for certain uses.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

9 Research Publications

Melatonin Ameliorates Depressive-Like Behaviors in Ovariectomized Mice by Improving Tryptophan Metabolism via Inhibition of Gut Microbe Alistipes Inops.

Animal

Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024

Researchers observed that melatonin can improve depressive-like behaviors in mice that underwent ovariectomy, a model for menopause. They found that melatonin works by altering gut bacteria, specifically reducing levels of a harmful microbe called Alistipes Inops, which negatively affects mood by disrupting tryptophan metabolism.

  • Melatonin reverses depressive-like behaviors in ovariectomized mice.
  • Melatonin treatment alters gut microbiota, reducing Alistipes Inops.
  • High levels of Alistipes Inops are linked to decreased tryptophan availability and depressive symptoms.
PubMed

Melatonin: the placental antioxidant and anti-inflammatory.

Review

Frontiers in immunology · 2024

Researchers found that melatonin, a hormone known for regulating sleep, plays a crucial role during pregnancy by acting as an antioxidant and anti-inflammatory agent in the placenta. This helps protect both the mother and fetus by reducing oxidative stress and maintaining a stable environment throughout gestation.

  • Melatonin is produced by the placenta, supporting its function during pregnancy.
  • It helps reduce oxidative stress by scavenging free radicals.
  • Melatonin regulates the immune system to support fetal development.
PubMed

Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders.

Review

Cellular and molecular neurobiology · 2023

Researchers observed that melatonin, a hormone primarily produced by the pineal gland, plays a crucial role in regulating sleep and circadian rhythms. They found that melatonin also has antioxidant properties and may help in managing various health issues, including mood disorders and cancer. Additionally, deficiencies in melatonin production are linked to several diseases.

  • Melatonin regulates sleep patterns and circadian rhythms.
  • It has antioxidant and anti-inflammatory properties.
  • Deficiencies in melatonin are associated with disorders like cancer and neurodegenerative diseases.
PubMed

Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder.

Human

Journal of the American Academy of Child and Adolescent Psychiatry · 2021

Researchers found that prolonged-release melatonin is safe and effective for treating insomnia in children with autism spectrum disorder over a two-year period. They observed improvements in sleep quality and caregiver satisfaction, with no negative effects on growth or puberty. The treatment was well-tolerated, with only mild side effects reported.

  • Improvements in sleep disturbance and caregiver satisfaction were maintained throughout the treatment.
  • No adverse effects on growth or pubertal development were observed.
  • Prolonged-release melatonin was generally safe, with mild side effects like fatigue and mood swings.
PubMed

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology.

Review

International journal of molecular sciences · 2020

Researchers observed that L-5-hydroxytryptophan (5-HTP) is a natural substance found in some dietary supplements and is produced in the body from tryptophan. They noted that 5-HTP is important for the production of serotonin, which is then converted into melatonin, a hormone that regulates sleep.

  • 5-HTP is both a natural component and a drug used in supplements.
  • It is produced from tryptophan by specific enzymes in the body.
  • 5-HTP plays a key role in the production of serotonin and melatonin.
PubMed

Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder.

Human

Journal of the American Academy of Child and Adolescent Psychiatry · 2017

Researchers found that prolonged-release melatonin minitablets improved sleep duration and reduced the time it took for children with autism spectrum disorder to fall asleep. After 13 weeks, children taking the melatonin slept an average of 57.5 minutes longer at night compared to those on a placebo. The melatonin was generally safe, with some participants experiencing increased drowsiness.

  • Children taking prolonged-release melatonin slept 57.5 minutes longer than those on placebo.
  • The time to fall asleep decreased by 39.6 minutes with melatonin compared to placebo.
  • 68.9% of children on melatonin showed significant improvement in sleep compared to 39.3% on placebo.
PubMed

A review of sleep disorders and melatonin.

Review

Neurological research · 2017

Researchers observed that sleep disorders can significantly impact daily life and current medications may lead to dependence and cognitive issues. They found that melatonin, a natural hormone, can effectively improve sleep quality and duration with fewer side effects, making it a promising alternative treatment for various sleep disorders.

  • Melatonin is well tolerated and has no significant short- or long-term side effects.
  • It helps synchronize circadian rhythms and improves sleep onset and quality.
  • Melatonin may serve as a safer alternative to traditional sleep medications.
PubMed

MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.

Review

Annual review of pharmacology and toxicology · 2016

Researchers found that melatonin, a hormone produced by the pineal gland, interacts with specific receptors (MT1 and MT2) to help regulate sleep, mood, and other health issues. They observed that new medications targeting these receptors could improve treatments for insomnia, mood disorders, and even cancer.

  • Melatonin levels vary throughout the day, being higher at night.
  • MT1 and MT2 receptors play a crucial role in sleep and mood regulation.
  • New melatonin-based medications are being developed to enhance treatment effectiveness.
PubMed

Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females.

Human

Journal of the International Society of Sports Nutrition · 2007

Researchers found that a single dose of 5.0 mg melatonin increased growth hormone levels in young males before and after resistance exercise while lowering somatostatin levels. Both doses of melatonin positively affected growth hormone levels during exercise, suggesting a beneficial interaction between melatonin and resistance training.

  • 5.0 mg melatonin increased growth hormone levels in males.
  • Melatonin reduced somatostatin levels before and after exercise.
  • Both doses of melatonin positively impacted growth hormone during resistance exercise.
PubMed

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This page is for informational and research purposes only. All information is based on published scientific literature. Nothing on this page constitutes medical advice or replaces consultation with a qualified healthcare professional.