%0 Journal Article %T Binding characterization of N©\(2©\chloro©\5©\thiomethylphenyl)©\N¡ä©\(3©\[3H]3methoxy phenyl)©\N¡ä©\methylguanidine ([3H]GMOM), a non©\competitive N©\methyl©\D©\aspartate (NMDA) receptor antagonist %A Albert D. Windhorst %A Athanasios Metaxas %A Bart N. M. van Berckel %A Emily C. Nash %A Esther J. M. Kooijman %A Johannes A. M. Christiaans %A Joost Verbeek %A Jos¨¦e E. Leysen %A Pieter J. Klein %A Ronald Boellaard %A Sandeep S. V. Golla %A V¨¦ronique A. Renja£¿n %J Archive of "Pharmacology Research & Perspectives". %D 2019 %R 10.1002/prp2.458 %X Labeled with carbon©\11, N©\(2©\chloro©\5©\thiomethylphenyl)©\N¡ä©\(3©\methoxyphenyl)©\N¡ä©\methylguanidine ([11C]GMOM) is currently the only positron emission tomography (PET) tracer that has shown selectivity for the ion©\channel site of N©\methyl©\D©\aspartate (NMDA) receptors in human imaging studies. The present study reports on the selectivity profile and in vitro binding properties of GMOM. The compound was screened on a panel of 80 targets, and labeled with tritium ([3H]GMOM). The binding properties of [3H]GMOM were compared to those of the reference ion©\channel ligand [3H](+)©\dizocilpine maleate ([3H]MK©\801), in a set of concentration©\response, homologous and heterologous inhibition, and association kinetics assays, performed with repeatedly washed rat forebrain preparations. GMOM was at least 70©\fold more selective for NMDA receptors compared to all other targets examined. In homologous inhibition and concentration©\response assays, the binding of [3H]GMOM was regulated by NMDA receptor agonists, albeit in a less prominent manner compared to [3H]MK©\801. Scatchard transformation of homologous inhibition data produced concave upward curves for [3H]GMOM and [3H]MK©\801. The radioligands showed bi©\exponential association kinetics in the presence of 100 ¦Ìmol L£¿1 l©\glutamate/30 ¦Ìmol L£¿1 glycine. [3H]GMOM (3 nmol L£¿1 and 10 nmol L£¿1) was inhibited with dual affinity by (+)©\MK©\801, (R,S)©\ketamine and memantine, in both presence and absence of agonists. [3H]MK©\801 (2 nmol L£¿1) was inhibited in a monophasic manner by GMOM under baseline and combined agonist conditions, with an IC50 value of ~19 nmol L£¿1. The non©\linear Scatchard plots, biphasic inhibition by open channel blockers, and bi©\exponential kinetics of [3H]GMOM indicate a complex mechanism of interaction with the NMDA receptor ionophore. The implications for quantifying the PET signal of [11C]GMOM are discussed %K [3H]GMOM %K [3H]MK©\801 %K binding %K ion©\channel %K N %K N¡ä©\diaryl©\N©\methylguanidine %K NMDA receptor %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381215/