Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

Alex R. Maolanon, Rune Risgaard, Shuang Yan Wang, Yoran Snoep, Athanasios Papangelis, Feng Yi, David Holley, Anne F. Barslund, Niels Svenstrup, Kasper B. Hansen, Rasmus P. Clausen

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.

OriginalsprogEngelsk
TidsskriftACS Chemical Neuroscience
Vol/bind8
Udgave nummer8
Sider (fra-til)1681-1687
Antal sider7
ISSN1948-7193
DOI
StatusUdgivet - 16 aug. 2017

ID: 183858151