BDNF and major depressive disorder: Despite its low affinity, REL-1017 remains trapped in the NMDAR selectivity pore similarly to ketamine and is therefore able to reduce excessive tonic Ca2+ currents, with downstream effects that restore synaptic proteins [40] and exert antidepressant-like effects in animal models [9], increase serum BDNF [35], and rapidly improve MDD in patients [13].