Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines
Article first published online: 1 JUL 2009
© 2009 The Authors. Journal compilation © 2009 John Wiley & Sons A/S
Journal of Pineal Research
Volume 47, Issue 2, pages 109–126, September 2009
How to Cite
Hardeland, R., Tan, D.-X. and Reiter, R. J. (2009), Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines. Journal of Pineal Research, 47: 109–126. doi: 10.1111/j.1600-079X.2009.00701.x
- Issue published online: 2 AUG 2009
- Article first published online: 1 JUL 2009
- Received May 27, 2009; accepted June 4, 2009.
- pyrrole ring cleavage;
- reactive nitrogen species;
- reactive oxygen species
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 N1,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.