Differential effects of five glycine site antagonists on NMDA receptor desensitisation.
The effects of five glycine site antagonists were comparatively examined on maximal and plateau currents evoked by 200 microM N-methyl-D-aspartate (NMDA) in the presence of 1 microM glycine in cultured cerebrocortical cells of the rat using whole-cell patch-clamp technique. 5,7-Dichlorokynurenic acid, ACEA-1021 (5-nitro-6,7-dichloro-quinoxalinedione), L-695,902 (methyl 7-chloro-4-hydroxy 2(1H)-quinolone-3-carboxylate), LY-294,619 (5,7-dichloro-3-(4-hydroxphenyl)-4-hydroxyquinolin-2(1H)-one ) and RPR-104,632 (2-(3-bromo-benzyl)-6,8-dichloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide-3-carboxylic acid) caused concentration-dependent inhibition of NMDA-activated currents. However, antagonists showed different relative efficacies to block peak currents and plateau currents, characterised by the following IC50 ratios: L-695,902: 0.98; RPR-104,632: 1.06; ACEA-1021: 1.69; LY-294,619: 1.71; and 5,7-dichlorokynurenic acid: 3.42. Our findings indicate a heterogeneity of glycine site antagonists in affecting NMDA receptor desensitisation, and suggest potential differences in their pharmacologies.
Molnár
P
P
CNS Pharmacology Laboratory, Chinoin Co. Ltd. Budapest, Hungary.
Erdõ
S L
SL
D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015363:Quinolones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D001581:Benzothiadiazines; D018691:Excitatory Amino Acid Antagonists; C103531:L 695902; C103529:LY 294619; D015363:Quinolones; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C103467:RPR 104632; C092062:licostinel; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine