Fig. 1: Memantine inhibition of AMPA receptors.

A Chemical structure of memantine. Representative current traces due to 10 mM glutamate in the absence (black) and presence of 500 µM memantine (pink) from HEK-293 cells expressing (B) GluA2(Q), (C) GluA2(Q)/γ2, (D) GluA2(Q)/γ8. E The dose-dependent inhibitory effects of memantine on GluA2 (Q)/γ2 with IC₅₀ 49 ± 2 µM (blue), and GluA2 (Q)/γ8 with IC₅₀ 48 ± 3 µM (pink). Each dot represents data from a different cell. F Representative current trace for GluA2(Q) due to 10 mM glutamate in the presence of 100 μM CTZ and in the absence (black) and presence of 500 µM memantine (pink). G The dose-dependent memantine inhibition on GluA2(Q) in the presence of CTZ at −60 (dark blue) and −100 mV (light blue), with IC₅₀ 48 ± 3 µM and 4.1 ± 1.3 µM, respectively. Each dot represents data from a different cell. H Single-channel currents were recorded from GluA2(Q) in the presence of 100 μM CTZ during continuous application of 10 mM glutamate alone (blue) and in the presence 500 µM of memantine (pink) at −100 mV. Openings are shown as downward deflections. I Amplitude histogram from the single channel recordings (n = 5). Effect of memantine under 10 Hz frequency stimulation with 10 mM glutamate alone (black) or in the presence of 10 µM of memantine (pink) for (J) GluA2(Q)/γ2 (n = 4) and (K) GluA2(Q)/γ8 (n = 4); p = 0.00023 and 0.00036 respectively. Data are shown as mean ± SEM. L Representative current trace for GluA2(R)/γ2 due to 10 mM glutamate in the absence (black) and presence of 500 µM memantine (pink). M The dose-dependent inhibitory effects of memantine on GluA2 (R)/γ2 with IC₅₀ 1129 ± 85 µM (blue), compared to GluA2 (Q)/γ2 with IC₅₀ 49 ± 2 µM (pink). Each dot represents data from a different cell.