GRIN1 and major depressive disorder: We therefore hypothesize that, when excessive tonic Ca2+ influx is corrected by an uncompetitive channel blocker with NR1-2D preference, such as REL-1017, the resolution of MDD symptomatology [13] may result from normalization of synaptic proteins that allow normal neural plasticity, as has been demonstrated in experimental models of depressive-like behavior using ketamine and REL-1017 [5,6,7,8,9].