TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner.

Neuropharmacology
S EdmanD J A Wyllie

Abstract

Antagonists that are sufficiently selective to preferentially block GluN2A-containing N-methyl-d-aspartate receptors (NMDARs) over GluN2B-containing NMDARs are few in number. In this study we describe a pharmacological characterization of 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl]benzyl]benzenesulphonamide (TCN 201), a sulphonamide derivative, that was recently identified from a high-throughput screen as a potential GluN2A-selective antagonist. Using two-electrode voltage-clamp (TEVC) recordings of NMDAR currents from Xenopus laevis oocytes expressing either GluN1/GluN2A or GluN1/GluN2B NMDARs we demonstrate the selective antagonism by TCN 201 of GluN2A-containing NMDARs. The degree of inhibition produced by TCN 201 is dependent on the concentration of the GluN1-site co-agonist, glycine (or D-serine), and is independent of the glutamate concentration. This GluN1 agonist-dependency is similar to that observed for a related GluN2A-selective antagonist, N-(cyclohexylmethyl)-2-[{5-[(phenylmethyl)amino]-1,3,4-thiadiazol-2-yl}thio]acetamide (TCN 213). Schild analysis of TCN 201 antagonism indicates that it acts in a non-competitive manner but its equilibrium constant at GluN1/GluN2A NMDARs indicates TCN 201 is aro...Continue Reading

References

Jun 30, 1992·Biochemical and Biophysical Research Communications·H SugiharaS Nakanishi
Apr 10, 1999·Nature Neuroscience·D D MottR Dingledine
May 31, 2002·Pharmacological Reviews·Arthur Christopoulos, Terry Kenakin
Mar 1, 1959·British Journal of Pharmacology and Chemotherapy·O ARUNLAKSHANA, H O SCHILD
Feb 11, 2005·Critical Reviews in Neurobiology·Kevin ErregerStephen F Traynelis
Feb 3, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jacques Neyton, Pierre Paoletti
Feb 14, 2006·British Journal of Pharmacology·Philip E Chen, David J A Wyllie
Jan 25, 2007·British Journal of Pharmacology·D J A Wyllie, P E Chen
Mar 18, 2008·Nature Neuroscience·Sofia PapadiaGiles E Hardingham
Jul 29, 2008·Neuropharmacology·Graham L CollingridgeMichael Spedding
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Francesc X SorianoGiles E Hardingham
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Sep 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Ezio BettiniFrancesca Cardullo
Oct 15, 2011·Trends in Pharmacological Sciences·Kevin K Ogden, Stephen F Traynelis
Nov 9, 2011·British Journal of Pharmacology·Stephen P H AlexanderJohn A Peters
May 4, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kasper B HansenStephen F Traynelis
May 15, 2012·Neuron·Marc-André MartelGiles E Hardingham

❮ Previous
Next ❯

Citations

Aug 27, 2013·Neuropharmacology·Sandra I MotaA Cristina Rego
Jul 19, 2014·The Journal of Clinical Investigation·Federico N SoriaMaría Domercq
Oct 30, 2014·Expert Opinion on Therapeutic Patents·Katie L StrongDennis C Liotta
Sep 27, 2012·Expert Opinion on Therapeutic Patents·Rose M SantangeloDennis C Liotta
Dec 19, 2015·Nature Communications·Jennifer StanicFabrizio Gardoni
Dec 20, 2015·The European Journal of Neuroscience·Hitoshi NaguraYoshinori Fujiyoshi
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Feb 5, 2013·Neuropharmacology·D J A WyllieG E Hardingham
Dec 3, 2014·Current Opinion in Pharmacology·Shujia Zhu, Pierre Paoletti
Oct 25, 2016·Neuropharmacology·David H Hackos, Jesse E Hanson
Dec 14, 2018·Brain : a Journal of Neurology·Vincent StrehlowUNKNOWN GRIN2A study group
Jan 18, 2018·Neuromolecular Medicine·Pradeep Punnakkal, Deity Dominic
Nov 22, 2014·The Journal of Pharmacology and Experimental Therapeutics·Yukitoshi Izumi, Charles F Zorumski
Dec 8, 2020·Frontiers in Neuroanatomy·Steffen GondaPetra Wahle
Oct 11, 2020·The Journal of Biological Chemistry·Veronica A CochraneShow-Ling Shyng
Nov 27, 2020·Neurobiology of Learning and Memory·Fernanda Troyner, Leandro Jose Bertoglio
Jan 18, 2021·The Journal of Biological Chemistry·Veronica A CochraneShow-Ling Shyng
Jul 18, 2021·Neuropharmacology·Alvaro Nuno-PerezManuel Mameli

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection

Software Mentioned

WinEDR
Microcal Origin

Related Concepts

Related Feeds

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is a form of of brain inflammation due to antibodies against NMDA receptors. Discover the latest research on anti-NMDA receptor encephalitis here.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.