Table 3.
EC50 Values for EU1180–55 Modulation of Triheteromeric NMDARsa
| Triheteromeric receptor | (S)-EU1180–55 | (R)-EU1180–55 | ||||
|---|---|---|---|---|---|---|
| EC50, μM (95% CI) | I(S)-EU180–55/ICONTROL, % | N | EC50, μM (95% CI) | I(R)-EU180–55/ICONTROL, % | N | |
| GluN1/GluN2A/GluN2A | b | b | 47 | b | b | 42 |
| GluN1/GluN2B/GluN2B | 4.3 (3.6–4.5) | 332 ± 18 | 37 | b | b | 37 |
| GluN1/GluN2C/GluN2C | 5.2 (4.2–6.3) | 384 ± 11 | 15 | 0.45 (0.38–0.54) | 230 ± 16 | 19 |
| GluN1/GluN2D/GluN2D | 8.0 (7.0–8.9) | 563 ± 31 | 8 | 1.4 (1.2–1.6) | 293 ± 26 | 11 |
| GluN1/GluN2A/GluN2B | 3.1 (2.7–3.5) | 200 ± 15 | 10 | b | b | 15 |
| GluN1/GluN2A/GluN2C | 3.0 (2.6–3.5) | 202 ± 13 | 13 | 1.3 (1.0–1.5) | 145 ± 4.8 | 16 |
| GluN1/GluN2A/GluN2D | 5.3 (4.8–5.9) | 369 ± 26 | 13 | 1.5 (1.2–1.9) | 156 ± 6.3 | 12 |
| GluN1/GluN2B/GluN2C | 4.9 (4.4–5.3) | 351 ± 14 | 10 | 1.5 (0.95–2.3) | 170 ± 11 | 8 |
| GluN1/GluN2B/GluN2D | 5.5 (5.0–6.2) | 458 ± 29 | 16 | 2.3 (2.0–2.6) | 158 ± 4.3 | 9 |
All chimeric GluN2 subunits contained the GluN2A C-terminal region plus C1 or C2 and an ER retention signal, as described in the Methods. All NMDAR currents were recorded in response to 100 μM glutamate and 30 μM glycine. The mean fitted EC50 value to 2 significant figures is given with the 95% confidence interval (CI) determined from the log (EC50 values). The mean ± SEM of the response to 30 μM test compound is given as a percent of the response in the absence of test drug to 3 significant figures. Non-overlapping confidence intervals were considered statistically significant. Hill slopes ranged from 0.6–2.6. N is the number of oocytes. For comparison, EC50 values from ref 69 for potentiation of wild-type diheteromeric NMDARs by (S)-EU1180–55 (compound S-(−)-2) were GluN1/GluN2A (no effect), GluN1/GluN2B (3.0 μM, maximum 276%), GluN1/GluN2C (3.1 μM, maximum 277%), GluN1/GluN2D (3.8 μM, maximum 267%). EC50 values from ref 69 for potentiation of wild-type diheteromeric NMDARs by (R)-EU1180–55 (compound R-(+)-2) were GluN1/GluN2A (no effect), GluN1/GluN2B (no effect), GluN1/GluN2C (0.71 μM, maximum 252%), GluN1/GluN2D (1.0 μM, maximum 297%).
No detectable effect.