Toxno Substance Profile
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Substance Name

Melatonin
Identification Number: CASRN | 73-31-4

  Substance Attributes


  • Metabolic Interference or Disruption

    Interferes with human metabolism. This can be a very serious thing. Some of these interference mechanics are well established. However, often long term effects and health consequences remain largely unknown. Additionally an emerging area of concern and one that is not currently studied, is the combined synergistic effects these metabolically disrupting chemicals have on human health.


    Metabolic interference happens when the substance produces highly reactive and often damaging intermediates during detoxification or when the substance binds to specific enzymes, important structural groups on molecules, receptors and membranes or targets DNA or mimics key nutrients.

  • Exposure Produces Health Symptoms

    Symptoms maybe short term or long term depending on the exposure duration and intensity and effects areas like Cardiovascular, Gastrointestinal, Cognition, Fatigue. A substance with this attribute may cause an allergic skin reaction, serious eye irritation, allergy or asthma symptoms or breathing difficulties if inhaled.

  • Has known Side Effects

    This is often the result of long or short term medication use. The same medication can have a range of side effects ranging from none at all to totally debilitating symptoms within different individuals. Reasons for this include individual genetics, individual detoxification capacity, nutrition status, duration of use and total number of medications being taken.


    It becomes very difficult to establish clear causes of symptoms when multiple medications are being taken at once.


    See SIDE EFFECTS LINKOUT at end of this profile.

These attributes are ONLY based on peer-reviewed evidence. See link to Data Sources below. Everyone benefits from knowing this stuff. Please Share.



  • CATEGORIES: Medication or Drug | Food Toxin | Natural Toxin | Plant Toxin | Animal Toxin | Medication Approved by the European Medicines Agency
  • SUBSTANCE LINEAGE: Organic Compounds | Heterocyclic Compounds | Indoles and Derivatives | Tryptamines and Derivatives | Serotonins
  • SYNONYMS: 5-Methoxy-N-acetyltryptamine | Circadin | Mela-T | Melatol | Melatonin (synth.) standard-grade | Melatonin (synth.) ultra-pure | Melatonine | Melovine | MT6 | N-(2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide | N-(2-(5-Methoxyindol-3-yl)ethyl)-Acetamide | N-(2-(5-Methoxyindol-3-yl)ethyl)acetamide | N-Acetyl-5-methoxy-tryptamine | N-Acetyl-5-methoxy-tryptamine Melatonine | N-Acetyl-5-methoxytryptamine | N-[2-(5-Methoxy-1H-indol-3-yl)ethyl)acetamide | N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]-Acetamide | N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide | N-[2-(5-Methoxyindol-3-yl)ethyl]-Acetamide | N-[2-(5-Methoxyindol-3-yl)ethyl]acetamide | Nature'S Harmony | Regulin | Revital Melatonin | Rx Balance | Sleep Right | Vivitas | {N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-} Acetamide | {N-[2-(5-methoxyindol-3-yl)ethyl]-} Acetamide
  • DESCRIPTION: Melatonin is a biogenic amine that is found in animals, plants and microbes. Aaron B. Lerner of Yale University is credited for naming the hormone and for defining its chemical structure in 1958. In mammals, melatonin is produced by the pineal gland. The pineal gland is small endocrine gland, about the size of a rice grain and shaped like a pine cone (hence the name), that is located in the center of the brain (rostro-dorsal to the superior colliculus) but outside the blood-brain barrier. The secretion of melatonin increases in darkness and decreases during exposure to light, thereby regulating the circadian rhythms of several biological functions, including the sleep-wake cycle. In particular, melatonin regulates the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature. Melatonin is also implicated in the regulation of mood, learning and memory, immune activity, dreaming, fertility and reproduction. Melatonin is also an effective antioxidant. Most of the actions of melatonin are mediated through the binding and activation of melatonin receptors. Individuals with autism spectrum disorders (ASD) may have lower than normal levels of melatonin. A 2008 study found that unaffected parents of individuals with ASD also have lower melatonin levels, and that the deficits were associated with low activity of the ASMT gene, which encodes the last enzyme of melatonin synthesis. Reduced melatonin production has also been proposed as a likely factor in the significantly higher cancer rates in night workers. Circadin is indicated as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over.
  • COMMENTS:
  • toxin chemical structure pubchem
  • FORMULA: C13H16N2O2
  • DATA SOURCES: DATA SOURCES: ARTICLE 4 | T3DB | PubChem | Drugbank | European Medicines Agency
  • LAST UPDATE: 28/04/2018

  Health Associations

Mostly focused on Health Implications of Long Term Exposure to this substance

  • SYMPTOMS: Loss of coordination, slowed reaction time, sleepiness and impaired judgment.
  • POSSIBLE HEALTH CONSEQUENCES: Tolerance can develop, in which the person needs larger doses to achieve the desired effect; this can lead to overdose and death. Accidents or injury can also occur due to the side effects of loss of coordination, slowed reaction time, sleepiness and impaired judgment. Drugs in this category have a high potential for physical and psychological dependence. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. | Hepatically metabolized to at least 14 identified metabolites (identified in mouse urine): 6-hydroxymelatonin glucuronide, 6-hydroxymelatonin sulfate, N-acetylserotonin glucuronide, N-acetylserotonin sulfate, 6-hydroxymelatonin, 2-oxomelatonin, 3-hydroxymelatonin, melatonin glucuronide, cyclic melatonin, cyclic N-acetylserotonin glucuronide, cyclic 6-hydroxymelatonin, 5-hydroxyindole-3-acetaldehyde, di-hydroxymelatonin and its glucuronide conjugate. 6-Hydroxymelatonin glucuronide is the major metabolite found in mouse urine (65-88% of total melatonin metabolites in urine). Half Life: 35 to 50 minutes
  • ACTION OF TOXIN: Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell. | Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate.
  • TOXIN SITES OF ACTION IN CELL: "Cytoplasm", "Extracellular"
  • Additional Exposure Routes: Used orally for jet lag, insomnia, shift-work disorder, circadian rhythm disorders in the blind (evidence for efficacy), and benzodiazepine and nicotine withdrawal. Evidence indicates that melatonin is likely effective for treating circadian rhythm sleep disorders in blind children and adults. It has received FDA orphan drug status as an oral medication for this use. A number of studies have shown that melatonin may be effective for treating sleep-wake cycle disturbances in children and adolescents with mental retardation, autism, and other central nervous system disorders. It appears to decrease the time to fall asleep in children with developmental disabilities, such as cerebral palsy, autism, and mental retardation. It may also improve secondary insomnia associated with various sleep-wake cycle disturbances. Other possible uses for which there is some evidence for include: benzodiazepine withdrawal, cluster headache, delayed sleep phase syndrome (DSPS), primary insomnia, jet lag, nicotine withdrawal, preoperative anxiety and sedation, prostate cancer, solid tumors (when combined with IL-2 therapy in certain cancers), sunburn prevention (topical use), tardive dyskinesia, thrombocytopenia associated with cancer, chemotherapy and other disorders.
  • SEE MEDICATION SIDE EFFECTS

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