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Author Notes:

Stephen F. Traynelis, 1510 Clifton Rd NE, Atlanta, GA, 30322, strayne@emory.edu, 404-727-0357

The authors contributed in the following manner: conceptualization (SFT, REP, SAS), data curation and formal analysis (REP, SAS, CS, AK, GFC, HY, SFT), funding acquisition (SAS, SFT, HY, DCL, GJB), investigation (REP, SAS, CS, AK, JZ, PL, EGA, GFC, MPE, DSM, PB), development or design of methodology (REP, SAS, SFT, EGA, GFC, MPE, GJB, DSM, DCL, LSL), project administration (REP, SFT, SAS), provision of reagents, materials, and analysis tools (PKRG, EGA, GFC, PB, GJB, MPE, DSM, DCL, LSL), software (REP, SFT), supervision (SFT, LSL, DCL, GJB), verification (REP, SAS, CS, AK, GFC, MPE, DSM), visualization and writing (all authors).

The authors thank Kevin Ogden for help with analytical software development.

SFT is a consultant for Janssen Pharmaceuticals Inc., is PI on a research grants from Janssen and Allergan to Emory University School of Medicine, is a member of the SAB for Sage Therapeutics, is co-founder of NeurOp Inc, and receives royalties for software. DCL is a member of the Board of Directors for NeurOp Inc. DCL, DSM, EGA, GFC, PKRG, LSL, MPE, SFT are co-inventors on Emory-owned Intellectual Property that includes allosteric modulators of NMDA receptor function. HY is PI on a research grant from Sage Therapeutics to Emory University School of Medicine.


Research Funding:

This work was supported by the NINDS (NS065371, SFT), NICHD (HD082373, HY), NIMH (MH109026, GB), Citizens United for Research in Epilepsy (SAS) and the Emory University Research Committee (SAS).


  • Allosteric modulator
  • ion channel
  • transitions rate
  • conformational state
  • open pore
  • N-methyl D-aspartate receptors (NMDARs)

Biased modulators of NMDA receptors control channel opening and ion selectivity

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Journal Title:

Nature Chemical Biology


Volume 16, Number 2


, Pages 188-196

Type of Work:

Article | Post-print: After Peer Review


Allosteric modulators of ion channels typically alter the transitions rates between conformational states without changing the properties of the open pore. We describe here a novel class of positive allosteric modulators of N-methyl D-aspartate receptors (NMDARs) that mediate a calcium-permeable component of glutamatergic synaptic transmission and play essential roles in learning, memory, cognition, as well as neurological disease. EU1622-14 increases agonist potency and channel open probability, slows receptor deactivation, in addition to decreasing both single channel conductance and calcium permeability. The unique functional selectivity of this chemical probe reveals a mechanism for enhancing NMDAR function while limiting excess calcium influx, and shows that allosteric modulators can act as biased modulators of ion channel permeation.
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