Table 3.
The maximal effects (Emax) and potencies (EC50) of compounds determined in two assays of D2R activation.a
| compound | D2R GPA GαoA | D2R mini Gsi recruitment | ||||
|---|---|---|---|---|---|---|
| pEC50 ± SEM | EC50 (nM) | Emax ± SEM (%) | pEC50 ± SEM | EC50 (nM) | Emax ± SEM (%) | |
| cariprazine | 8.87 ± 0.08 | 1.35 | 94.2 ± 1.7 | 8.87 ± 0.28 | 1.34 | 22.5 ± 1.7 |
| 13a | 8.77 ± 0.10 | 1.70 | 94.7 ± 2.2 | 8.65 ± 0.27 | 2.26 | 18.4 ± 1.4 |
| 11b | 7.37 ± 0.19 | 42.60 | 41.4 ± 3.0 | ND | ND | ND |
| 13b | 8.22 ± 0.10 | 5.98 | 75.0 ± 2.3 | ND | ND | ND |
| 6c | 9.57 ± 0.15 | 0.27 | 102.3 ± 3.6 | 8.39 ± 0.06 | 4.10 | 92.4 ± 1.6 |
| 13c | 9.13 ± 0.13 | 0.75 | 96.4 ± 3.3 | 7.96 ± 0.06 | 11.02 | 90.6 ± 2.0 |
| 11d | <7 | >100 | <60% | ND | ND | ND |
| 13d | 7.57 ± 0.15 | 27.12 | 64.3 ± 3.2 | ND | ND | ND |
| 6e | 8.14 ± 0.14 | 7.18 | 74.3 ± 3.1 | ND | ND | ND |
| 7e | 8.30 ± 0.11 | 5.00 | 95.9 ± 2.9 | 8.15 ± 0.43 | 7.08 | 11.1 ± 1.9 |
| 13e | 8.28 ± 0.11 | 5.22 | 93.0 ± 2.9 | 7.58 ± 0.21 | 26.21 | 12.5 ± 0.9 |
| 21a | 8.40 ± 0.10 | 3.97 | 95.9 ± 2.8 | 7.93 ± 0.12 | 11.86 | 36.7 ± 1.5 |
| 22a | 8.20 ± 0.06 | 6.28 | 94.5 ± 1.9 | 7.66 ± 0.11 | 21.85 | 25.1 ± 0.9 |
| 22b | 7.96 ± 0.08 | 10.89 | 86.7 ± 2.4 | 8.00 ± 0.18 | 9.92 | 15.4 ± 1.0 |
| Quinpirole | 9.03 ± 0.05 | 0.93 | 100.1 ± 1.3 | 7.40 ± 0.08 | 39.78 | 100.0 ± 2.7 |
| Dopamine | - | - | - | 7.18 ± 0.03 | 66.25 | 99.9 ± 1.1 |
a
Compounds were tested in an amplified GαoA G protein (GPA GαoA) activation assay, shown on the left columns, and a less amplified miniG recruitment assay, shown on the right columns. ND indicates no agonist response detected, ‘-’ indicates compound not tested. Data represent the mean ± SEM of three independent experiments performed in duplicate.