Table 1.

Listing of the reference NMDAR modulators.

Compounds	Modulator	Selectivity	Action	References
D-AP5	Competitive antagonist	GluN2A	Inhibits excitatory response. Impacts behavioral learning; blocks plasticity (LTP).	[95,96,97]
Riluzole	Competitive antagonist	GluN1/GluN2B	Indirect block of NMDAR. Protects from motor deficit.	[103,104,105]
Phencyclidine	Selective uncompetitive antagonist	GluN2B/D(PCP site)	Induces psychotic and dissociative schizophrenia-like symptoms. Impairs NMDAR neurotransmission in vivo.	[98]
Ketamine	Uncompetitive antagonist	GluN2B/D(PCP site)	Applied in post-synapse: inhibits excitatory pyramidal neuron in extra-synaptic GluN2B. Applied in pre-synapse: inhibits GluN2D in interneuron (induces disinhibition of Glu release in post-synapse). Up-regulates hippocampal AMPARs (GluA1/GluA2). Antidepressant.	[100,106]
Dizocilpine	Uncompetitive antagonist	GluN2A/B/D(PCP site)	Anticonvulsant, antidepressant. Induces memory impairments.	[102,107]
Ifenprodil	Uncompetitive antagonist	GluN1/GluN2B(N-Terminal domain)	Blocks GluN2B (140-fold preference for NR2B over NR2A subunits). Induces inhibition of GluN2R receptor currents. Anti-Parkinsonian effect.	[108,109,110]
Memantine	Uncompetitive antagonist	GluN1/GluN2B	Blocks GluN2B extra-synaptic and induces glutamatergic excitotoxicity. Used for moderate-to-severe AD.	[111,112]
Amantadine	Uncompetitive antagonist	GluN1/GluN2B	Blocks GluN1/GluN2B by accelerating channel closure during channel block. Used as anti-Parkinsonian drug.	[113]
Dextromethorphan	Uncompetitive antagonist	GluN2A	Blocks GluN2A subunit. Prevents neuronal damage and modulates pain sensation	[114,115,116,117,118]