Modulation of the kynurine pathway of tryptophan metabolism in search for neuroprotective agents. Focus on kynurenine-3-hydroxylase.
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.
Pellicciari
Roberto
R
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Amori
Laura
L
Costantino
Gabriele
G
Giordani
Antonio
A
Macchiarulo
Antonio
A
Mattoli
Luisa
L
Pevarello
Paolo
P
Speciale
Carmela
C
Varasi
Mario
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005849:Gerbillinae; D006801:Humans; D066298:In Vitro Techniques; D007737:Kynurenine / Q000378:metabolism*; D050601:Kynurenine 3-Monooxygenase; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D014364:Tryptophan / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D007737:Kynurenine; D014364:Tryptophan; D006899:Mixed Function Oxygenases; D050601:Kynurenine 3-Monooxygenase