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

Judit Füvesi, Csaba Somlai, Hajnalka Németh, Hedvig Varga, Zsolt Kis, Tamás Farkas, Norbert Károly, Márton Dobszay, Zsuzsa Penke, Botond Penke, László Vécsei, József Toldi

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Evoked cortical responses
  • Excitatory amino acids
  • Glucosamine-kynurenic acid
  • Kynurenic acid
  • Neuronal protection
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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