Putative cognition enhancers reverse kynurenic acid antagonism at hippocampal NMDA receptors
| Autor: | Maurizio Raiteri, Anna Pittaluga, Roberto Pattarini |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Pyrrolidines Glycine In Vitro Techniques Pharmacology Kynurenic Acid Kynurenate Hippocampus Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley Norepinephrine chemistry.chemical_compound Cognition Kynurenic acid medicine Animals Oxiracetam Glutamate receptor antagonist Psychotropic Drugs Chemistry Glutamate receptor Glutamic acid Pyrrolidinones Rats Aniracetam Biochemistry Cycloserine NMDA receptor medicine.drug |
| Zdroj: | European Journal of Pharmacology. 272:203-209 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(94)00641-j |
| Popis: | Oxiracetam, aniracetam and D-cycloserine, three putative cognition enhancers, were examined in a functional assay for NMDA receptors. Rat hippocampal slices or synaptosomes were labeled with [3H]noradrenaline and exposed to NMDA or glutamate in superfusion. NMDA (100 microM) elicited a remarkable rise (about 500%) in the release of [3H]noradrenaline from slices. The effect of NMDA was antagonized by the glutamate receptor blocker, kynurenic acid. The antagonism by 100 microM kynurenate was reduced by submicromolar concentrations of oxiracetam and totally reversed by 1 microM of the drug. The concentration-antagonism curve for kynurenic acid was shifted to the right in the presence of 0.2 or 1 microM oxiracetam. Aniracetam and D-cycloserine, as well as glycine and D-serine, behaved similarly to oxiracetam: all compounds, tested at 1 microM, reversed the antagonism by 100 microM kynurenate of the NMDA-evoked [3H]noradrenaline release. In superfused hippocampal synaptosomes, 100 microM NMDA or glutamic acid elicited the release of [3H]noradrenaline; the evoked release was enhanced by glycine, but not by oxiracetam. In this preparation 1 microM glycine or 1 microM oxiracetam prevented the antagonism by kynurenate of the NMDA- or the glutamate-evoked [3H]noradrenaline release. As kynurenic acid is an endogenous glutamate receptor antagonist whose brain levels are known to increase in conditions associated to cognitive deficits, it is proposed that the putative cognition enhancers tested may act in vivo by relieving the antagonism produced by excessive endogenous kynurenate. |
| Databáze: | OpenAIRE |
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