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CNS Drugs
Erschienen in: CNS Drugs 2/2009

01.02.2009 | Leading Article

Pharmacological Manipulation of Kynurenic Acid

Potential in the Treatment of Psychiatric Disorders

verfasst von: Dr Sophie Erhardt, Sara K. Olsson, Göran Engberg

Erschienen in: CNS Drugs | Ausgabe 2/2009

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Abstract

The kynurenine pathway constitutes the main route of tryptophan degradation and generates the production of several neuroactive compounds; quinolinic acid is an excitotoxic NMDA receptor agonist, 3-hydroxykynurenine is a free-radical generator and kynurenic acid (KYNA) is an antagonist at glutamate and nicotinic receptors. In low micromolar concentrations, KYNA blocks the glycine site of the NMDA receptor and the nicotinic α7* acetylcholine receptor. Knowledge regarding kynurenine metabolites and their involvement in neurophysiological processes has increased dramatically in recent years. In particular, endogenous KYNA appears to tightly control firing of midbrain dopamine neurons and to be involved in cognitive functions. Thus, decreased endogenous levels of rat brain KYNA have been found to reduce firing of these neurons, and mice with a targeted deletion of kynurenine aminotransferase II display low endogenous brain KYNA levels concomitant with an increased performance in cognitive tests. It is also suggested that kynurenines participate in the pathophysiology of psychiatric disorders. Thus, elevated levels of KYNA have been found in the CSF as well as in the post-mortem brain of patients with schizophrenia. Advantages in understanding how kynurenines can be pharmacologically manipulated may provide new possibilities in the treatment of psychiatric disorders, such as schizophrenia.
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Metadaten
Titel
Pharmacological Manipulation of Kynurenic Acid
Potential in the Treatment of Psychiatric Disorders
verfasst von
Dr Sophie Erhardt
Sara K. Olsson
Göran Engberg
Publikationsdatum
01.02.2009
Verlag
Springer International Publishing
Erschienen in
CNS Drugs / Ausgabe 2/2009
Print ISSN: 1172-7047
Elektronische ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200923020-00001

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