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.
Original language | English |
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Pages (from-to) | 1681-1687 |
Number of pages | 7 |
Journal | ACS Chemical Neuroscience |
Volume | 8 |
Issue number | 8 |
DOIs | |
State | Published - Aug 16 2017 |
Keywords
- Ionotropic glutamate receptor
- NMDA
- d -cycloserine
- d -serine
- subtype selectivity
- superagonist