Kynurenic acid antagonists and kynurenine pathway inhibitors

The kynurenine pathway accounts for the metabolism of around 80% of non-protein tryptophan metabolism. It includes both an agonist (quinolinic acid) at NMDA receptors and an antagonist (kynurenic acid). Since their discovery, there has been a major development of kynurenic acid analogues as neuroprotectants for the treatment of stroke and neurodegenerative disease. Several prodrugs of kynurenic acid or its analogues that can be hydrolysed within the CNS are also available. More recently, the pathway itself has proved to be a valuable drug target, affected by agents which reduce the synthesis of quinolinic acid and increase the formation of kynurenic acid. The change in the balance of these, away from the excitotoxin and towards the neuroprotectant, has anticonvulsant and neuroprotective properties.