A contribution to the structure-activity relationship in glutamate receptor ligands: 1. omega-Aminophosphonic acids do not antagonize NMDA receptors.
Pharmacological properties of a series of alpha, omega-diamino-omega-phosphonocarboxylic acids and alpha, omega-diamino-alpha, omega-bis(phosphonic acids) on different excitatory amino acids mediated responses have been tested in CA1 rat hippocampal neurones, using intracellular recordings and current and voltage clamp techniques. In contrast with known antagonists as D(-)2-amino-5-phosphonopentanoic acid (AP-5) and 2-amino-4-oxo-5-phosphonopentanoic acid, which completely abolished the NMDA-response, no antagonistic activity was found. We conclude that the introduction of an omega-amino function abolishes the NMDA-antagonistic activity of alpha-amino-omega-phosphonocarboxylic acids.
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
D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D008024:Ligands; D063065:Organophosphonates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate