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1 The potency of two novel glycine site antagonists, GV150,526A and GV196,771A, was assessed by their ability to inhibit the binding of [ 3 H]-MDL105,519 to cell homogenates prepared from mammalian cells transfected with either NR1-1a, NR1-2a, NR1-1a/NR2A, NR1-1a/NR2B, NR1-1a/ NR2C or NR1-1a/NR2D NMDA receptor clones. 2 The inhibition constants (K i s) for GV150,526A displacement of [ 3 H]-MDL105,519 binding to either NR1-1a or NR1-2a expressed alone were not signi®cantly dierent and were best ®t by a onesite binding model. GV150,526A inhibition to NR1-1a/NR2 combinations was best ®t by a two-site model with the NR1-1a/NR2C having an approximate 2 ± 4 fold lower anity compared to other NR1-1a/NR2 receptors. 3 The K i s for GV196,771A displacement of [ 3 H]-MDL105,519 binding to NR1-1a, NR1-2a and all NR1-1a/NR2 combinations was best ®t by a two-site binding model. There was no signi®cant dierence between the K i s for the binding to NR1-1a and NR1-2a; NR1-1a/NR2A receptors had an approximate 4 fold lower anity for GV196,771A compared to other NR1-1a/NR2 combinations. 4 The K i s for both GV150,526A and GV196,771A for the inhibition of [ 3 H]-MDL105,519 binding to membranes prepared from adult rat forebrain were determined and compared to the values obtained for binding to cloned NMDA receptors. 5 The K i s for a series of glycine site ligands with diverse chemical structures were also determined for the inhibition of [ 3 H]-MDL105,519 binding to NR1-1a/NR2A receptors. L689,560 displayed similar binding characteristics to GV150,526A. 6 It is suggested that glycine site antagonists may be divided into two classes based on their ability to distinguish between NR1 and NR1/NR2 receptors with respect to binding curve characteristics.

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