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

Roberto Pellicciari; Laura Amori; Gabriele Costantino; Antonio Giordani; Antonio Macchiarulo; Luisa Mattoli; Paolo Pevarello; Carmela Speciale; Mario Varasi

doi:10.1007/978-1-4615-0135-0_71

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.

Authors

Roberto Pellicciari¹, Laura Amori, Gabriele Costantino, Antonio Giordani, Antonio Macchiarulo, Luisa Mattoli, Paolo Pevarello, Carmela Speciale, Mario Varasi

Affiliation

¹ Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.

PMID: 15206781
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