TABLE 9.

Distinct mechanisms of action of NMDA receptor modulators

Selectivity	Mode of Action	Modulator	Open Probability †	Glutamate EC50	Glycine EC50	Tau Deact	Unitary Conductance	Ionic Permeability
GluN2A	NAM	TCN-201	–	NE	↑	↑	–	–
GluN2A	PAM	GNE-8324	↑	↓	NE	↑	–	–
GluN2B	NAM	ifenprodil	↓	↓	–	↑	NE	–
GluN2C	PAM	PYD-106	↑	↓	NE	↑	NE	–
GluN2C/D	NAM	QNZ-46	↓	↓	NE	↑	NE	–
GluN2C/D	PAM	(+)-CIQ	↑	NE	NE*	NE*	NE	–
pan	NAM#	EU1794-4	↑	↓	↓	↑	↓	↓ pCa /pNa
pan	PAM	EU1622-14	↑	↓	↓	↑	↓	↓ pCa /pNa
pan	PAM	(S)-EU1180-55	↑	↓	↓	↑	NE	NE
pan	PAM	GNE-9278	↑	↓	↓	↑	–	–
pan	PAM	PTC-174	↑ (2A ↓)	↓	↓	↑	–	–
pan	PAM	EU-1794-27	↑ (2A ↓)	↓	↓	↑	–	–

– denotes no available data, NE denotes no effect.

* (+)-CIQ had an effect only on GluN1/2C.

^† Open probability was estimated from the overall effect on macroscopic peak responses and assumed no change in single-channel conductance or number of active receptors.

^# EU1794-4 increased open probability but decreased single channel conductance, and the overall net effect was a reduction in macroscopic current, hence the designation of NAM (Perszyk et al., 2018; Perszyk et al., 2021).

↑ and ↓ indicate that the measured parameter was reported to be significantly greater than or less than the response in the absence of modulator and was used when either statistical tests were reported or reported values did not have overlapping confidence intervals.