Table 4.
Time dependent D3R pharmacological profile of quinpirole and AB04-88.
| Quinpirole | AB04-88 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Go Protein Activation | β-arrestin Recruitment | Bias Factors | Go Protein Activation | β-arrestin Recruitment | Bias Factors | |||||
| Time-points (min) | pEC50 ± SEM | Emax (% of quinpirole) | pEC50 ± SEM | Emax (% of quinpirole) | pEC50 ± SEM | Emax (% of quinpirole) | pEC50 ± SEM | Emax (% of quinpirole) | ||
| 2 | 8.51 ± 0.25 | 101 ± 5.6 | 8.20 ± 0.26 | 92.8 ± 3.9 | 0.4 | 9.20 ± 0.21 | 112.7 ± 5.8 | 7.64 ± 0.12 | 94.4 ± 1.4 | 1.6 |
| 4 | 8.72 ± 0.14 | 101.4 ± 2.0 | 8.23 ± 0.23 | 97.9 ± 1.9 | 0.5 | 9.27 ± 0.14 | 113.8 ± 3.3 | 7.57 ± 0.08 * | 96.4 ± 0.2 | 1.8 |
| 6 | 8.81 ± 0.13 | 102.3 ± 1.0 | 8.21 ± 0.19 | 100.3 ± 1 | 0.6 | 9.32 ± 0.12 | 114.0 ± 1.6 | 7.43 ± 0.07 ** | 99.1 ± 0.2 | 1.9 |
| 8 | 8.86 ± 0.13 | 101.4 ± 0.4 | 8.13 ± 0.14 | 100.6 ± 0.3 | 0.7 | 9.37 ± 0.12 | 112.9 ± 0.6 | 7.30 ± 0.09 *** | 101.3 ± 0.1 | 2.1 |
| 10 | 8.91 ± 0.14 | 100.0 ± 0.0 | 8.07 ± 0.12 | 100.0 ± 0 | 0.8 | 9.39 ± 0.12 | 111.7 ± 0.0 | 7.20 ± 0.13 *** | 102.2 ± 0 | 2.3 |
| 12 | 8.94 ± 0.14 | 98.9 ± 0.3 | 8.04 ± 0.10 | 99.4 ± 0.3 | 0.9 | 9.40 ± 0.11 | 110.0 ± 0.5 | 7.16 ± 0.15 *** | 101.8 ± 0.9 | 2.3 |
| 14 | 8.96 ± 0.15 | 97.3 ± 0.6 | 8.01 ± 0.11 | 98.3 ± 0.6 | 0.9 | 9.40 ± 0.10 | 108.9 ± 0.8 | 7.14 ± 0.16 *** | 100.7 ± 1.8 | 2.3 |
| 16 | 8.97 ± 0.15 | 95.6 ± 0.9 | 7.97 ± 0.11 | 97.0 ± 0.9 | 1.0 | 9.39 ± 0.10 | 107.6 ± 1.2 | 7.13 ± 0.14 *** | 100.2 ± 2.8 | 2.3 |
| 18 | 8.98 ± 0.15 | 94.2 ± 1.1 | 7.94 ± 0.12 | 95.9 ± 1.3 | 1.0 | 9.39 ± 0.10 | 106.4 ± 1.5 | 7.13 ± 0.13 *** | 99.1 ± 3.3 | 2.3 |
| 20 | 8.99 ± 0.14 | 93.5 ± 1.2 | 7.92 ± 0.14 | 95.5 ± 1.5 | 1.0 | 9.39 ± 0.08 | 105.3 ± 1.7 | 7.14 ± 0.12 ** | 98.4 ± 3.5 | 2.3 |
| 22 | 8.99 ± 0.15 | 92.6 ± 1.4 | 7.92 ± 0.14 | 94.5 ± 1.7 | 1.0 | 9.40 ± 0.08 | 104.0 ± 1.9 | 7.15 ± 0.14** | 97.1 ± 3.8 | 2.3 |
| 24 | 9.00 ± 0.15 | 91.8 ± 1.6 | 7.86 ± 0.18 | 93.9 ± 1.9 | 1.1 | 9.38 ± 0.07 | 104.6 ± 2.1 | 7.17 ± 0.14 ** | 96.2 ± 4.5 | 2.2 |
| 26 | 9.00 ± 0.14 | 90.9 ± 1.6 | 7.89 ± 0.14 | 93.1 ± 1.9 | 1.1 | 9.36 ± 0.09 | 104.2 ± 2.3 | 7.20 ± 0.13 ** | 94.6 ± 5.1 | 2.2 |
| 28 | 9.03 ± 0.13 | 91.1 ± 1.9 | 7.87 ± 0.15 | 93.4 ± 1.9 | 1.1 | 9.35 ± 0.09 | 105.3 ± 3.1 | 7.20 ± 0.11 * | 94.0 ± 6.1 | 2.2 |
| 30 | 9.06 ± 0.12 | 91.0 ± 2.3 | 7.91 ± 0.10 | 93.1 ± 2.2 | 1.1 | 9.36 ± 0.08 | 105.3 ± 4.0 | 7.21 ± 0.11 ** | 93.0 ± 6.4 | 2.2 |
| 32 | 9.03 ± 0.13 | 91.6 ± 2.6 | 7.94 ± 0.08 | 93.1 ± 2.5 | 1.1 | 9.35 ± 0.06 | 108.0 ± 4.8 | 7.24 ± 0.11 ** | 92.1 ± 7.6 | 2.2 |
| 34 | 9.03 ± 0.13 | 93.3 ± 3.5 | 7.96 ± 0.07 | 94.3 ± 3.2 | 1.1 | 9.30 ± 0.08 | 111.6 ± 5.5 | 7.25 ± 0.13 ** | 90.6 ± 6.9 | 2.1 |
| 36 | 9.00 ± 0.15 | 94.7 ± 4.3 | 7.99 ± 0.06 | 94.7 ± 3.9 | 1.0 | 9.30 ± 0.07 | 116.2 ± 6.6 | 7.23 ± 0.15 ** | 89.7 ± 6.7 | 2.2 |
| 38 | 9.03 ± 0.15 | 95.8 ± 4.1 | 7.99 ± 0.05 | 95.1 ± 3.1 | 1.0 | 9.26 ± 0.09 | 121.3 ± 7.7 * | 7.23 ± 0.15 ** | 88.5 ± 6.0 | 2.2 |
| 40 | 8.99 ± 0.16 | 98.6 ± 4.8 | 7.97 ± 0.05 | 96.2 ± 3.5 | 1.0 | 9.27 ± 0.07 | 125.3 ± 9.4 * | 7.25 ± 0.14 ** | 87.6 ± 6.8 | 2.2 |
| 42 | 9.00 ± 0.15 | 102.5 ± 6.2 | 7.96 ± 0.03 | 97.6 ± 4.3 | 1.1 | 9.24 ± 0.07 | 134.6 ± 12.5 ** | 7.32 ± 0.09 * | 85.9 ± 6.9 | 2.1 |
| 44 | 9.05 ± 0.13 | 105.2 ± 8.7 | 7.96 ± 0.04 | 98.0 ± 6.5 | 1.1 | 9.24 ± 0.06 | 145.6 ± 17.3 **** | 7.31 ± 0.08 * | 85.4 ± 6.8 | 2.2 |
| 46 | 9.19 ± 0.17 | 112.0 ± 10.9 | 7.99 ± 0.07 | 100.6 ± 5.2 | 1.3 | 9.23 ± 0.09 | 160.0 ± 23.6 **** | 7.25 ± 0.09 ** | 84.9 ± 6.6 | 2.3 |
pEC50 ± SEM values and Emax values at both D3R mediated G protein activation and β-arrestin recruitment assays at time-points ranging from 2–46 min are reported. Bias factors, calculated as described in Section 2, are also reported. The bias factor values ≥ 2.0 are highlighted in orange. Using Sidak’s multiple comparisons tests, statistical significance are reported as ‘*’ representing significance of p < 0.05; ‘**’ of p < 0.01; ‘***’ of p < 0.001 and ‘****’ of p < 0.0001 compared to that of quinpirole.