Comparative study on the effects of kynurenic acid and glucosamine-kynurenic acid.
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.
Füvesi
Judit
J
Department of Comparative Physiology, University of Szeged, P.O. Box 533, H-6701, Szeged, Hungary.
Somlai
Csaba
C
Németh
Hajnalka
H
Varga
Hedvig
H
Kis
Zsolt
Z
Farkas
Tamás
T
Károly
Norbert
N
Dobszay
Márton
M
Penke
Zsuzsa
Z
Penke
Botond
B
Vécsei
László
L
Toldi
József
J
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005944:Glucosamine / Q000737:chemistry* / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007736:Kynurenic Acid / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007736:Kynurenic Acid; D005944:Glucosamine