The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives

Russel J. Reiter, Dun Xian Tan, Sergio Rosales-Corral, Lucien C. Manchester

Research output: Contribution to journalArticlepeer-review

252 Scopus citations


Melatonin is an uncommonly widely distributed molecule. It is found throughout the plant and animal kingdoms, i.e., perhaps in every living organism. Within vertebrate organisms, melatonin also has an extremely wide distribution, seemingly being capable of entering every cell and all subcellular compartments. So-called morphophysiological barriers, e.g., the blood-brain barrier, are no impediment to the passage of melatonin and it has a multitude of confirmed functions. We have hypothesized that melatonin originally evolved as a free radical scavenger and during evolution it acquired other important and essential actions. Due to the multi-faceted actions of melatonin and its metabolites as direct free radical scavengers and indirect antioxidants, these agents have been used to abate oxidative damage in a diverse variety of experimental models where free radical destruction is a component. When compared with classic, better-known antioxidants, melatonin is better in terms of limiting destruction of intracellular macromolecules when the damage is a consequence of excessive oxygen or nitrogen-based toxic reactants. Considering the vast array of experimental data that has accumulated which documents melatonin's high efficacy and lack of, or minimal, toxicity over a very wide dose range, it is essential that the usefulness of this agent be more thoroughly tested at the clinical level. The findings from experimental models of numerous diseases overwhelming confirm that this indoleamine would likely have great benefit in aiding humans suffering with conditions that have as their basis tissue and molecular damage resulting from oxygen and nitrogen-based reactants.

Original languageEnglish (US)
Pages (from-to)373-384
Number of pages12
JournalMini-Reviews in Medicinal Chemistry
Issue number3
StatePublished - 2013


  • Animals
  • Free radicals
  • Intracellular concentrations
  • Melatonin
  • Oxidative stress
  • Plants

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology


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