Kynurenines in the CNS: from endogenous obscurity to therapeutic importance

In just under 20 years the kynurenine family of compounds has developed from a group of obscure metabolites of the essential amino acid tryptophan into a source of intensive research, with postulated roles for quinolinic acid in neurodegenerative disorders, most especially the AIDS-dementia complex and Huntington's disease. One of the kynurenines, kynurenic acid, has become a standard tool for use in the identification of glutamate-releasing synapses, and has been used as the parent for several groups of compounds now being developed as drugs for the treatment of epilepsy and stroke. The kynurenines represent a major success in translating a basic discovery into a source of clinical understanding and therapeutic application, with around 3000 papers published on quinolinic acid or kynurenic acid since the discovery of their effects in 1981 and 1982. This review concentrates on some of the recent work most directly relevant to the understanding and applications of kynurenines in medicine.