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-

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-aspartate (NMDA) antagonists acting at different sites of the NMDA receptor complex on NMDA-induced currents in Xenopus oocytes expressing heteromeric NR1A/NR2A and NR1A/NR2B receptors. The polyamine site antagonists eliprodil (IC₅₀=3.0 μM) and ifenprodil (IC₅₀=0.27 μM) antagonized NMDA responses at NR1A/NR2B receptors but not at NR1A/NR2A receptors (IC₅₀>100 μM). 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

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-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 effect profile.