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Comparative study on the effects of kynurenic acid and glucosamine–kynurenic acid

Füvesi, Judit and Somlai, Csaba and Németh, Hajnalka and Varga, Hedvig and Kis, Zsolt and Farkas, Tamás and Károly, Norbert and Dobszay, Márton and Penke, Zsuzsa and Penke, Botond and Vécsei, László and Toldi, József (2004) Comparative study on the effects of kynurenic acid and glucosamine–kynurenic acid. Pharmacology Biochemistry and Behavior, 77 (1). pp. 95-102. ISSN 0091-3057

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Abstract

Kynurenic acid (KYNA) is the only known endogenous N-methyl-d-aspartate (NMDA) receptor inhibitor and might therefore come into consideration as a therapeutic agent in certain neurobiological disorders. However, its use as a neuroprotective compound is practically excluded because KYNA does not readily cross the blood-brain barrier (BBB). We recently synthetized a new compound, glucosamine–kynurenic acid (KYNA-NH-GLUC), which is presumed to cross the BBB more easily. In this study, the effects of KYNA and KYNA-NH-GLUC on behavior and cortical activity were investigated in adult rats. The results show that (1) on intracerebroventricular application, the behavioral changes induced by KYNA and by KYNA-NH-GLUC are quite similar; (2) on intravenous administration, KYNA (25 mg/kg) has no effect on the somatosensory-evoked cortical potentials, whereas KYNA-NH-GLUC (25 mg/kg) causes transient but appreciable reductions in the amplitudes of the evoked responses within 5 min after application; and (3) the results of in vitro studies demonstrated that both KYNA and KYNA-NH-GLUC reduced the amplitudes of the field excitatory postsynaptic potentials (fEPSPs). These observations suggest that the two compounds have similar effects, but that KYNA-NH-GLUC passes the BBB much more readily than does KYNA. These results imply that the conjugated NH-GLUC is of importance in the passage across the BBB.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: Erika Bilicsi
Date Deposited: 21 Sep 2012 09:18
Last Modified: 14 Jan 2014 11:26
URI: http://real.mtak.hu/id/eprint/3034

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