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. 2023 Nov 7;33(4):355–373. doi: 10.1093/hmg/ddad188

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© The Author(s) 2023. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Rescue pharmacology of GluD1 and GluD2 constitutively active variants using FDA-approved channel blockers in Xenopus oocytes. (A) Pentamidine composite concentration-response curves for GluD2 variants show that pentamidine has an IC₅₀ value that is > 200 fold lower (i.e. more potent) for GluD2-T649A (IC₅₀ 37 nM) than for GluD2-A654T. Recordings were performed in 1 mM Ca²⁺. (B) Structures of compounds tested in this study are shown. (C and D) Results are shown for a single concentration screen for memantine (C) and ketamine (D) inhibition of GluD receptor channel constitutive activity. (E) Memantine concentration-response curves are shown for GluD2-A654D and GluD2-A654T.