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Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites.

ABSTRACT: 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.

SUBMITTER: Maolanon AR

PROVIDER: S-EPMC5559341 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites.

Maolanon Alex R AR Risgaard Rune R Wang Shuang-Yan SY Snoep Yoran Y Papangelis Athanasios A Yi Feng F Holley David D Barslund Anne F AF Svenstrup Niels N Hansen Kasper B KB Clausen Rasmus P RP

ACS chemical neuroscience 20170530 8

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 ...[more]

PMID: 28514141

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