A contribution to the structure-activity relationship in glutamate receptor ligands: 2. Characterization of 2-amino-4-oxo-5-pentanoic acid as NMDA receptor antagonist.
Pharmacological properties of 2-amino-4-oxo-5-phosphonopentanoic acid (AOPA) on excitatory amino acids mediated responses have been tested in CA1 rat hippocampal neurones, using intracellular recordings and current and voltage clamp techniques. These properties were compared with those of the well-known NMDA antagonist, D(-)2-amino-5-phosphonopentanoic acid (AP-5). AOPA completely abolished the response to NMDA but had no effects on the responses to AMPA, quisqualate and kainate. In voltage clamp experiments AOPA antagonized NMDA-induced currents and produced a parallel shift of the NMDA concentration-response curve. Schild analysis gave a Kd value of 26 microM. AP-5 also produced a similar shift in this curve with a Kd of 6.9 mu.
Ito
S
S
INSERM Unité 029, Paris, France.
Van Assche
I
I
Soroka
M
M
Haemers
A
A
Ben Ari
Y
Y
Cherubini
E
E
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007982:Levulinic Acids / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D007982:Levulinic Acids; D008024:Ligands; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C080941:2-amino-4-oxo-5-phosphonopentanoic acid; D016202:N-Methylaspartate