In summary, under certain pathological conditions (e.g., MDD), uncompetitive NMDAR antagonists can be characterized not only as “activity-dependent” [29] but as “hyperactivity-dependent” and therefore NMDAR subtypes most sensitive to pathological activation (i.e., GluN2D) are more likely to be blocked [43,51]. The gene discussed is GRIN2D; the disease is major depressive disorder.