Table 2.
Pharmacological comparison of bitopic ligands at D2R.
| D2R, 10 min | Go Protein Activation Assay | β-arrestin Recruitment | ||||||
|---|---|---|---|---|---|---|---|---|
| Compounds | Emax ± SEM (% of Quinpirole) | pEC50 ± SEM | Change Emax over Quinpirole | Fold Potency over Quinpirole |
Emax ± SEM (% of Quinpirole) | pEC50 ± SEM | Change Emax over Quinpirole | Fold Potency over Quinpirole |
| Quinpirole | 100 ± 2.0 | 7.46 ± 0.07 | 0.00 | 1.00 | 100 ± 2.8 | 6.93 ± 0.08 | 0.0 | 1.00 |
| rac-FOB02-04 | 93.2 ± 2.2 | 7.13 ± 0.06 * | −6.80 | 0.47 | 62.9 ± 1.9 **** | 5.72 ± 0.07 **** | −37.1 | 0.06 |
| FOB02-04A | 91.2 ± 2.8 | 7.31 ± 0.08 | −8.80 | 0.71 | 60.4 ± 1.9 **** | 6.04 ± 0.07 **** | −39.6 | 0.13 |
| FOB02-04B | 81.4 ± 3.8 *** | 6.44 ± 0.13 **** | −18.60 | 0.10 | 56.9 ± 1.4 **** | 5.45 ± 0.05 **** | −43.1 | 0.03 |
| AB04-87 | ND | ND | ND | ND | ND | ND | ND | ND |
| AB04-88 | 95.2 ± 2.4 | 7.25 ± 0.07 | −4.80 | 0.62 | 72.6 ± 2.6 **** | 5.84 ± 0.06 **** | −27.4 | 0.08 |
| rac-AB04-35 | 75.9 ± 5.3 *** | 6.48 ± 0.13 **** | −24.10 | 0.10 | 102.8 ± 2.5 | 5.74 ± 0.06 **** | 2.80 | 0.06 |
| AB04-95 | ND | ND | ND | ND | ND | ND | ND | ND |
| AB04-96 | 102.7 ± 4.0 | 7.28 ± 0.11 | 2.70 | 0.66 | 121.6 ± 8.2 *** | 6.14 ± 0.13 **** | 21.6 | 0.16 |
Mean Emax ± SEM and pEC50 ± SEM values along with fold changes over quinpirole are reported. Using Dunnett’s multiple comparisons tests, statistical significance are reported as ‘*’ representing significance of p < 0.05; ‘***’ of p < 0.001 and ‘****’ of p < 0.0001 compared to quinpirole. ND, not determined.