TABLE 2.
Affinity and selectivity of existing clinically used and novel β-AR ligands as determined from antagonism of cimaterol-induced 3H-cAMP accumulation in CHO-β1, CHO-β2, or CHO-β3 cells
| Compound | Human β1-AR |
Human β2-AR |
Human β3-AR |
β1
vs. β2 selectivity |
|||||
|---|---|---|---|---|---|---|---|---|---|
| Log Kd,β1 | n | Schild slope | n | Log Kd,β2 | n | Log Kd,β3 | n | Kd,β2/Kd,β1 | |
| Bisoprolol | −8.60 ± 0.03 | 15 | 0.97 ± 0.03 | 5 | −6.76 ± 0.03 | 13 | −5.65 ± 0.06 | 5 | 69 |
| Carvedilol | −9.75 ± 0.12 | 12 | 1.29 ± 0.09 | 4 | −10.62 ± 0.08 | 4 | −8.54 ± 0.18 | 3 | 0.13 |
| Nebivolol | −9.28 ± 0.08 | 22 | 1.15 ± 0.03 | 5 | −7.91 ± 0.09 | 11 | −6.35 ± 0.06 | 9 | 23 |
| CGP20712A | −9.64 ± 0.03 | 15 | 1.03 ± 0.03 | 5 | −6.02 ± 0.03 | 8 | −5.47 ± 0.04 | 5 | 4169 |
| NDD-713 | −8.52 ± 0.03 | 12 | 1.06 ± 0.03 | 4 | −5.44 ± 0.03 | 4 | −5.47 ± 0.08 | 3 | 1202 |
| NDD-825 | −8.99 ± 0.05 | 9 | 1.04 ± 0.02 | 3 | −5.75 ± 0.06 | 4 | −5.72 ± 0.08 | 7 | 1738 |
The Schild slope is that obtained in CHO-β1 cells from the rightward shift of the cimaterol dose-response curve by 3 different concentrations of antagonist in the same experiment (e.g., Fig. 3) where a value of 1 represents competitive antagonism. The affinity of most ligands at β2-AR and β3-AR was too low to allow a Schild plot to be constructed. Values shown are means ± sem of n separate experiments.