Comparative study on the effects of kynurenic acid and glucosamine–kynurenic acid
- 作者：Fü ; vesi ; Judit ; Somlai ; Csaba ; Né ; meth ; Hajnalka ; Varga ; Hedvig ; Kis ; Zsolt ; Farkas ; Tamá ; s ; et. al.
- 关键词：Excitatory amino acids ; Evoked cortical responses ; Glucosamine&ndash ; kynurenic acid ; Kynurenic acid ; Rat ; Neuronal protection
- 刊名：Pharmacology Biochemistry and Behavior
- 出版年：2004
- 期刊代码：219_00913057
- 类别：med
- 出版时间：January, 2004
- 卷：77
- 期：1
- 页码：95-102
- 文件大小：295 K
摘要
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.