Stereoselective enhancement by (R)-HA-966 of the binding of [3H]CPP to the NMDA receptor complex.
The enantiomers of the strychnine-insensitive glycine antagonist, HA-966 (1-hydroxy-3-amino-pyrrolidone-2), stereoselectively enhance binding of the N-methyl-D-aspartate (NMDA) competitive antagonist, [3H]CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) to rat brain synaptosomal membranes. The enhancement by the more potent (R)-HA-966 is competitively inhibited by the glycine antagonist 7-chlorokynurenic acid and noncompetitively by the polyamine spermine. Thus, (R)-HA-966, apparently at the glycine site, enhances the binding of antagonist to the NMDA receptor, possibly through a mechanism partially in common with that of spermine.
Pullan
L M
LM
ICI Pharmaceuticals Group, ICI Americas, Inc., Wilmington, DE 19897.
Powel
R J
RJ
Stumpo
R J
RJ
Britt
M
M
Klika
A B
AB
Meiners
B A
BA
Salama
A I
AI
D000818:Animals; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism; D013237:Stereoisomerism; D013331:Strychnine / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D010879:Piperazines; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; D013331:Strychnine; C057013:7-chlorokynurenic acid