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

J Pineal Res. 2009 Sep;47(2):109-26. doi: 10.1111/j.1600-079X.2009.00701.x. Epub 2009 Jul 1.

Abstract

Kynuramines represent their own class of biogenic amines. They are formed either by decarboxylation of kynurenines or pyrrole ring cleavage of indoleamines. N(2)-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),N(1)-dimethylated analogs, including indirect effects via release of catecholamines or acetylcholine and interference with serotonin receptors. After the discovery of N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) and N(1)-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.

Publication types

  • Review

MeSH terms

  • Animals
  • Biogenic Amines / metabolism*
  • Humans
  • Indoles / metabolism*
  • Kynuramine / analogs & derivatives
  • Kynuramine / metabolism*
  • Melatonin / metabolism*
  • Models, Molecular

Substances

  • Biogenic Amines
  • Indoles
  • Kynuramine
  • N-acetyl-N-formyl-5-methoxykynurenamine
  • N-acetyl-5-methoxy kynurenamine
  • Melatonin