title: Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines.
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.
authors: Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany.
authors: Rüdiger
authors: R
authors: Hardeland
authors: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.
authors: Dun-Xian
authors: DX
authors: Tan
authors: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.
authors: Russel J
authors: RJ
authors: Reiter
mesh_terms: D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D007735:Kynuramine / Q000031:analogs & derivatives / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism*; D008958:Models, Molecular
chemical_list: D001679:Biogenic Amines; D007211:Indoles; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; C032131:N-acetyl-5-methoxy kynurenamine; D008550:Melatonin