Potency, dissociation, and post hoc association values of mAChR antagonists using a [Ca2+]i-flux or ERK1/2 phosphorylation assay under hemi-equilibrium conditions
Data are expressed as mean ± S.D. from a single fit to grouped data of three to four individual experiments.
| pKB from hemi-equilbrium model | pKB from Schild analysis | koff (min−1) | Post hoc kon | t1/2 | ||
|---|---|---|---|---|---|---|
| ×107 M−1min−1 | min | |||||
| 4-DAMP | 8.06 ± 0.14 | 7.89 ± 0.18 | nd | nd | <2 | [Ca2+]i-flux assay |
| Atropine | 9.44 ± 0.08 | 9.10 ± 0.30 | 0.05 ± 0.01 | 14.3 ± 4.96 | 14.2 ± 2.4 | |
| Himbacine | 6.51 ± 0.16 | 6.62 ± 0.20 | nd | nd | <2 | |
| Ipratropium | 9.73 ± 0.10 | 9.40 ± 0.12 | 0.05 ± 0.01 | 26.7 ± 12.7 | 14.9 ± 15.7 | |
| NMS | 9.85 ± 0.11 | 9.24 ± 0.16 | 0.02 ± 0.01 | 16.0 ± 10.2 | 33.9 ± 4.4 | |
| Pirenzepine | 7.80 ± 0.11 | 7.21 ± 0.15 | 0.03 ± 0.01 | 0.21 ± 0.09 | 23.3 ± 7.7 | |
| Atropine | 9.23 ± 0.21 | 8.88 ± 0.15 | 0.03 ± 0.01 | 20.0 ± 28.4 | 27.1 ± 1.0 | ERK1/2 phosphorylation assay |
| Glycopyrrolate | 10.09 ± 0.12 | 9.83 ± 0.18 | 0.007 ± 0.002 | 9.66 ± 7.93 | 98.8 ± 32.4 | |
| QNB | 9.89 ± 0.08 | 10.19 ± 0.22 | 0.003 ± 0.001 | 1.90 ± 0.96 | 272 ± 103 | |
| Tiotropium | 10.25 ± 0.26 | 9.74 ± 0.51 | 0.003 ± 0.002 | 3.53 ± 3.42 | 223 ± 84.9 |
nd, not determined; QNB, quinuclidinyl benzylate.