Figure 1. NMDA receptor activities with GluN1 partial agonists.

a, Crystal structures of the GluN1 ligand-binding domain in complex with the full agonist Gly (PDB:1PB7), the partial agonist DCS (PDB:1PB9) and the antagonist DCKA (PDB: 1PBQ) suggested that full and partial agonists induce the same degree of cleft closure relative to the open structure stabilized by antagonist²⁷. b, Chemical structure of the agonist used is shown to the left of a representative single-channel trace (10 s displayed filter at 1 kHz with openings down). Glutamate (1 mM) was included in all recordings alongside saturating concentrations of the indicated co-agonist. Underlined portion (500 ms) of each record is expanded below filtered at 12 kHz. c, Histograms of closed interval distributions for a record in each condition (events: Gly, 509,041; Ala, 317,593; DCS, 31,754) are overlaid with probability density function (thick lines) and exponential components E₁ – E₅ (thin lines) calculated from fits of the 5C3O state model to the entire sequence of events in the respective file. Insets show time constants and areas for the corresponding exponential components in the file shown. Bottom panel illustrates together the E₂ and E₃ components for the three agonists above. *Efficacy reported by refs. ²⁶ and ²⁵.