Kynuramines, metabolites of melatonin and other indoles: The resurrection of an almost forgotten class of biogenic amines

Rüdigger Hardeland, Dun Xian Tan, Russel J. Reiter

Research output: Contribution to journalReview articlepeer-review

370 Scopus citations

Abstract

Kynuramines represent their own class of biogenic amines. They are formed either by decarboxylation of kynurenines or pyrrole ring cleavage of indoleamines. N2-formylated compounds formed in this last reaction can be deformylated either enzymatically by arylamine formamidases or hemoperoxidases, or photochemically. The earlier literature mainly focussed on cardiovascular effects of kynuramine, 5-hydroxykynuramine and their N 1,N1-dimethylated analogs, including indirect effects via release of catecholamines or acetylcholine and interference with serotonin receptors. After the discovery of N1-acetyl-N2-formyl-5- methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) as major brain metabolites of melatonin, these compounds became of particular interest. They were shown to be produced enzymatically, pseudoenzymatically, by various free radical-mediated and via photochemical processes. In recent years, AFMK and AMK were shown to scavenge reactive oxygen and nitrogen species, thereby forming several newly discovered 3-indolinone, cinnolinone and quinazoline compounds, and to protect tissues from damage by reactive intermediates in various models. AMK is of special interest due to its properties as a potent cyclooxygenase inhibitor, NO scavenger forming a stable nitrosation product, inhibitor and/or downregulator of neuronal and inducible NO synthases, and a mitochondrial metabolism modulator. AMK easily interacts with aromates, forms adducts with tyrosyl and tryptophanyl residues, and may modify proteins.

Original languageEnglish (US)
Pages (from-to)109-126
Number of pages18
JournalJournal of pineal research
Volume47
Issue number2
DOIs
StatePublished - Sep 2009

Keywords

  • 5-hydroxykynuramine
  • AFMK
  • AMK
  • Inflammation
  • Mitochondria
  • Pyrrole ring cleavage
  • Reactive nitrogen species
  • Reactive oxygen species

ASJC Scopus subject areas

  • Endocrinology

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