New advances in NMDA receptor pharmacology

• Type of Material: Article
• Authors: Kevin K. Ogden, Emory University; Stephen Traynelis, Emory University
• Language: English
• Date: 2011-12
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016%2Fj.tips.2011.08.003
• Title of Journal or Parent Work: Trends in Pharmacological Sciences
• ISSN: 0165-6147
• Volume: 32
• Issue: 12
• Start Page: 726
• End Page: 733
• Grant/Funding Information: This work was supported by NINDS (NS036654, NS065371 SFT), NIGMS (GM008602 KKO), and NIDA (DA015040 KKO).
• Research Categories: Health Sciences, Pharmacology

Abstract

N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia, and schizophrenia. The GluN2 subunits contribute substantially to functional diversity of NMDA receptors and are distinctly expressed in development and among brain regions. Thus, subunit-selective antagonists and modulators that differentially target the GluN2 subunit might provide an opportunity to pharmacologically modify the function of select groups of neurons for therapeutic gain. A flurry of clinical, functional, and chemical studies have together reinvigorated efforts to identify subunit-selective modulators of NMDA receptor function, resulting in a handful of new compounds that appear to act at novel sites. Here we review the properties of new emerging classes of subunit-selective NMDA receptor modulators, which we predict will mark the beginning of a productive period of progress for NMDA receptor pharmacology.