Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites

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A series of analogues based on serine as lead structure were designed, and their agonist activities were evaluated at recombinant NMDA receptor subtypes (GluN1/2A-D) using two-electrode voltage-clamp (TEVC) electrophysiology. Pronounced variation in subunit-selectivity, potency, and agonist efficacy was observed in a manner that was dependent on the GluN2 subunit in the NMDA receptor. In particular, compounds 15a and 16a are potent GluN2C-specific superagonists at the GluN1 subunit with agonist efficacies of 398% and 308% compared to glycine. This study demonstrates that subunit-selectivity among glycine site NMDA receptor agonists can be achieved and suggests that glycine-site agonists can be developed as pharmacological tool compounds to study GluN2C-specific effects in NMDA receptor-mediated neurotransmission.

Original languageEnglish
JournalACS Chemical Neuroscience
Issue number8
Pages (from-to)1681-1687
Number of pages7
Publication statusPublished - 16 Aug 2017

    Research areas

  • d -cycloserine, d -serine, Ionotropic glutamate receptor, NMDA, subtype selectivity, superagonist

ID: 183858151