β1-, β2-, or β3-AR functional potency values, selectivity ratios and β2-AR intrinsic efficacy values for a range of β2-AR agonists determined in cAMP detection assays
All pEC50 data shown were generated in the LANCE cAMP assay and used to determine selectivity ratios between the β-AR subtypes. β2-AR intrinsic efficacy data were generated in the fluorescence polarization cAMP assay. To determine the intrinsic efficacy the fitted maximum asymptote for the test drug was divided by that obtained for isoprenaline. Data are presented as mean ± S.E.M. for at least four separate determinations. P values were determined via ANOVA and were adjusted using the Holm (1979) method.
| β2-AR Agonist | β2 | β1 | Selectivity Ratio | β3 | Selectivity Ratio | β2 Intrinsic Efficacy |
|---|---|---|---|---|---|---|
| pEC50 | pEC50 | β2 over β1 | pEC50 | β2 over β3 | ||
| Vilanterol | 10.37 ± 0.05 | 6.98 ± 0.03 | 2400 | 7.36 ± 0.03 | 1000 | 0.70 ± 0.03 |
| Salmeterol | 9.80 ± 0.10* | 6.32 ± 0.12 | 3000 | 6.48 ± 0.13 | 2100 | 0.41 ± 0.01*** |
| Formoterol | 10.14 ± 0.08 | 7.96 ± 0.03 | 150*** | 8.36 ± 0.03 | 59*** | 0.95 ± 0.04*** |
| Indacaterol | 9.48 ± 0.08* | 8.28 ± 0.04 | 16*** | 8.16 ± 0.03 | 20*** | 0.86 ± 0.02*** |
| Salbutamol | 7.31 ± 0.03* | 5.87 ± 0.03 | 27*** | 6.33 ± 0.06 | 9.5*** | N.D. |
| Isoprenaline | 8.43 ± 0.02* | 9.04 ± 0.02 | 0.24*** | 8.56 ± 0.02 | 0.74*** | 1*** |
N.D., not determined.
↵* P < 0.05 versus vilanterol;
*** P < 0.0001 versus vilanterol.