7-Chlorokynurenate prevents NMDA-induced and kainate-induced striatal lesions.
NMDA-induced lesions of striatal cholinergic interneurons were attenuated by 7-chlorokynurenate (7-ClKyn), an antagonist of the glycine site of the NMDA receptor complex. However, it was not possible to demonstrate clearly that the mechanism of action of 7-ClKyn was in fact antagonism of the glycine site. Thus, the agonists at the glycine site, D-serine and 1-aminocyclopropane-1-carboxylic acid, failed to reverse the protection afforded by 7-ClKyn. Finally, 7-ClKyn also protected against lesions produced by kainate. The selectivity of 7-ClKyn under intracerebral administration is apparently insufficient for determining the role of the glycine site in NMDA-receptor mediated excitotoxicity.
Lehmann
J C
JC
Groupe de Recherche Servier, Puteaux, France.
Procureur
D
D
Wood
P L
PL
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000517:prevention & control; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012694:Serine / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D007608:Kainic Acid