NPS 1506, a moderate affinity uncompetitive NMDA receptor antagonist: preclinical summary and clinical experience

NPS Pharmaceuticals, Inc. (NPS) has synthesized a series of open-channel blockers with varying potencies at the NMDA receptor. NPS 1506 (Fig. 1) is a moderate affinity antagonist that inhibits NMDA/glycine-induced increases in cytosolic calcium in cultured rat cerebellar granule cells (IC50 = 476 nM) and displaces the binding of [3H]MK-801 to rat cortical membranes (IC50 = 664 nM).