Pharmacology of the kynurenine pathway

The kynurenine pathway of tryptophan oxidative metabolism plays a major role in the nervous and immune systems and has been implicated in a range of disease states. Much of the interest in the pathway has been centred around the role of quinolinic acid as an agonist at glutamate receptors sensitive to N-methyl-d-aspartate (NMDA) and kynurenic acid which blocks all the ionotropic glutamate receptors. In addition, it is clear that the pathway is important in modulating the level of oxidative stress in tissues, partly via the activation of blockade of NMDA receptors, but also via the generation of redox active compounds such as 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Pharmacological interference with this pathway therefore presents a route for reducing oxidative tissue damage at several different metabolic steps, providing a valuable potential therapeutic target for new drug development.