Modulation of the kynurine pathway of tryptophan metabolism in search for neuroprotective agents. Focus on kynurenine-3-hydroxylase

Adv Exp Med Biol. 2003:527:621-8. doi: 10.1007/978-1-4615-0135-0_71.

Abstract

A novel potent and selective kynurenine-3-hydroxylase inhibitor is descibed along a preliminary evaluation in a in vivo gerbil model of its ability to increase the kynurenine and kynurenic acid concentration in both plasma and brain. These data support the notion that kynurenine-3-hydroxylase inhibitors may have a sustained therapeutic potential in those diseases characterized by unbalance in the QUIN/KYNA branches of the kynurenine pathway.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Gerbillinae
  • Humans
  • In Vitro Techniques
  • Kynurenine / metabolism*
  • Kynurenine 3-Monooxygenase
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Mixed Function Oxygenases / chemistry
  • Models, Molecular
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Protein Conformation
  • Tryptophan / metabolism*

Substances

  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Kynurenine
  • Tryptophan
  • Mixed Function Oxygenases
  • Kynurenine 3-Monooxygenase