Fig. 2: A permanently charged memantine derivative does not exhibit MCI.
From: Inhibition of NMDA receptors through a membrane-to-channel path
a TMM, which exists in aqueous solution only in a charged form. b Recording protocol (left) used to measure traditional [TMM]-inhibition curve (right) at pH 7.2. TMM traditional IC50 = 72.3 ± 14.2 μM, n = 4. c DMM, which exists in charged and uncharged forms in aqueous solution (pKa estimated computationally; see text). d Recording protocol (left) used to measure the traditional [DMM]-inhibition curve (right) at pH 7.2. DMM traditional IC50 = 16.8 ± 1.5 μM, n = 8. e MCI protocol performed with 1 mM TMM at pH 9.0. f MCI protocol performed with 165 μM DMM at pH 9.0. In overlays in e and f, traces following TMM or DMM application are red. g Min IMCI/IControl for 30 μM memantine (0.327 ± 0.024, n = 9) in pH 9.0 jump experiments, and of 1 mM TMM (0.987 ± 0.039, n = 7) and 165 μM DMM (0.402 ± 0.037, n = 5) at constant pH 9.0. Min IMCI/IControl values compared to 1 with two-tailed t-test. Values are different from 1 for memantine (t = −11.0, df = 3, p = 0.0016) and DMM (t = −16.2, df = 4, p = 0.000086), but not for TMM (t = −0.339, df = 6, p = 0.75). Min IMCI/IControl values compared with one-way ANOVA (F(2,18) = 16.1, p = 0.000099) and Tukey post-hoc test (memantine vs TMM, p = 0.00011; memantine vs DMM, p = 0.82; TMM vs DMM, p = 0.0019). In b, d, g, mean ± SEM is plotted.
