Subtype-Specific Agonists for NMDA Receptor Glycine Binding Sites

ACS Chemical Neuroscience
Alex R MaolanonRasmus P Clausen

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.

References

Jul 14, 2000·Journal of Medicinal Chemistry·H Bräuner-OsborneP Krogsgaard-Larsen
Mar 20, 2003·Behavioural Brain Research·Gernot RiedelJacques Micheau
Jul 28, 2004·Molecular Psychiatry·D C Javitt
Aug 22, 2006·Biological Psychiatry·Michael DavisRick Richardson
Feb 19, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shashank M DravidStephen F Traynelis
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Apr 28, 2011·Nature Communications·Katie M VanceHiro Furukawa
Apr 30, 2013·Molecular Pharmacology·Kasper B HansenStephen F Traynelis
Jan 28, 2014·Neuron·Annie JespersenHiro Furukawa
May 31, 2014·Science·Erkan Karakas, Hiro Furukawa

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Citations

Jul 25, 2018·The Journal of General Physiology·Kasper B HansenStephen F Traynelis
Nov 14, 2019·International Journal of Molecular Sciences·Iulia Zoicas, Johannes Kornhuber
Jun 1, 2021·Neuropharmacology·David StroebelPierre Paoletti

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