A novel kynurenic acid analogue a comparison with kynurenic acid. An in vitro electrophysiological study /

Kynurenic acid is an endogenous product of the tryptophan metabolism, and as a broad-spectrum antagonist of excitatory amino acid receptors may serve as a protective agent in neurological disorders. The use of kynurenic acid as a neuroprotective agent is rather limited, however, because it has only...

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Elmentve itt :
Bibliográfiai részletek
Szerzők: Marosi Máté Gábor
Nagy Dávid
Farkas Tamás
Kis Zsolt
Rózsa Éva
Robotka Hermina
Fülöp Ferenc
Vécsei László
Toldi József
Dokumentumtípus: Cikk
Megjelent: Springer-Verlag 2010
Sorozat:JOURNAL OF NEURAL TRANSMISSION 117 No. 2
doi:10.1007/s00702-009-0346-2

mtmt:1308187
Online Access:http://publicatio.bibl.u-szeged.hu/9928
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520 3 |a Kynurenic acid is an endogenous product of the tryptophan metabolism, and as a broad-spectrum antagonist of excitatory amino acid receptors may serve as a protective agent in neurological disorders. The use of kynurenic acid as a neuroprotective agent is rather limited, however, because it has only restricted ability to cross the blood-brain barrier. Accordingly, new kynurenic acid analogues which can readily cross the blood-brain barrier and exert their complex anti-excitotoxic activity are greatly needed. Such a novel analogue, 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride, has been developed and tested. In an in vitro electrophysiological study, in which its properties were compared with those of kynurenic acid, the new analogue behaved quite similarly to kynurenic acid: in the micromolar range, its administration led to a decrease in the amplitudes of the field excitatory postsynaptic potentials in the CA1 region of the hippocampus, while in nanomolar concentrations it did not give rise to inhibition, but, in fact, facilitated the field excitatory postsynaptic potentials. Moreover, the new analogue demonstrated similar protective action against PTZ-induced facilitation to that observed after kynurenic acid administration. The findings strongly suggest that the neuroactive effects of the new analogue are comparable with those of kynurenic acid, but, in contrast with kynurenic acid, it readily crosses the blood-brain barrier. The new analogue may therefore be considered a promising candidate for clinical studies. 
700 0 1 |a Nagy Dávid  |e aut 
700 0 1 |a Farkas Tamás  |e aut 
700 0 1 |a Kis Zsolt  |e aut 
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700 0 1 |a Robotka Hermina  |e aut 
700 0 1 |a Fülöp Ferenc  |e aut 
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700 0 1 |a Toldi József  |e aut 
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