Clinical Neuroscience - 2000;53(1-2 Különszám)

Clinical Neuroscience

JANUARY 01, 2000

[Kynurenine in the central nervous system: the "kynurenic acid test" and cognition enhancers]

VÉCSEI László

[Brain tissue can synthetize L-kynurenine from tryptophan, but L-kynurenine can also be transported across the blood-brain-barrier. lnterest in kynurenine has increased markedly since it became clear that two of its metabolic products quinolinic acid and kynurenic acid, act as agonist and antagonist, respectively, at receptors for excitatory amino acids. lntracerebroventricular (icv) microinjected kynurenic acid induced dose-dependent increases in ataxia and stereotyped behavior, while equimolar kynurenine has only slight effects on these neurological parameters, at least in the administered doses. D-Serine partially inhibited but did not eliminate kynurenic acid-induced neurological abnormalities when administered icv in high doses. Our findings show that D-serine can partially antagonize the neurological abnormalities induced by kynurenic acid. This is consistent with a predominant effect of kynurenic acid at the glycine allosteric site on the NMDA receptor complex at physiological concentrations. Some putative cognition enhancers (oxiracetam, aniracetam and Dcycloserine) were shown to prevent the kynurenic acid antagonism of the N-methyl-D-aspartate (NMDA)-evoked norepinephrine release in rat hippocampal slices. Drugs active in the "kynurenate test" may bind to sites different from the glycine site of the NMDA receptor. To conclude, the "kynurenate test" is an in vitro assay useful in the identitication and characterization of putative cognition enhancers acting via NMDA receptors]

HUN 2000;53(1-2 Különszám)