Antagonist properties of eliprodil and other NMDA receptor antagonists at rat NR1A/NR2A and NR1A/NR2B receptors expressed in Xenopus oocytes.
We have studied the effects of a variety of N-methyl-D-aspartate (NMDA) antagonists acting at different sites of the NMDA receptor complex on NMDA-induced currents in Xenopus oocytes expressing heteromeric NR1A/NR2 and NR1A/NR2B receptors. The polyamine site antagonists eliprodil (IC50 = 3.0 microM) and ifenprodil (IC50 = 0.27 microM) antagonized NMDA responses at NR1A/NR2B receptors but not at NR1A/NR2A receptors (IC50 > 100 microM). The channel blockers dizocilpine, memantine and phencyclidine (PCP) were equally potent antagonists at both receptor subtypes whereas dextromethorphan was four times more potent at NR1A/NR2A receptors. The glycine site antagonists L-689,560 and 7-Cl-kynurenate were 10 times more potent at NR1A/NR2A than at NR1A/NR2B receptor subtypes. The selectivity of eliprodil and ifenprodil for the NR1A/NR2B receptor subtype may, at least partially, explain their favorable side effects profile.
Avenet
P
P
Synthélabo Recherche, Bagneux, France.
Léonardon
J
J
Besnard
F
F
Graham
D
D
Depoortere
H
H
Scatton
B
B
D000818:Animals; D001665:Binding Sites; D004553:Electric Conductivity; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D014981:Xenopus
D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C058083:eliprodil