“…Subsequent determination of K B from Schild analysis suggested that the selectivity was only ϳ5-fold, precluding its use as a selective tool (Frizelle et al, 2006;Neyton and Paoletti, 2006). Antagonists with bulky, hydrophobic substituents, such as phenanthrene-piperazine dicarboxylic acid analogs (2S,3R)-1-(phenanthren-2-carbonyl)piperazine-2,3-dicarboxylic acid and (2R,3S)-1-(phenanthrenyl-3-carbonyl)piperazine-2,3-dicarboxylic acid (UBP141), show only modest 10-fold higher affinity for GluN2C-and GluN2D-containing receptors over GluN2A andGluN2B (Feng et al, 2004, 2005;Morley et al, 2005;Costa et al, 2009) (Table 11). Subunit selectivity for competitive antagonists may be difficult to achieve because of high homology among GluN2 subunit LBDs.…”