Competition binding affinities, equilibrium association, and dissociation kinetics using the Motulsky and Mahan (1984) method determined using [3H]NMS and cLogD7.4 values of the mAChR antagonists used within this study
Data are expressed as mean ± S.D. from a single fit to grouped data of three to six individual experiments. cLogD7.4 values were obtained using ChemAxon MarvinSketch software as described in Materials and Methods.
| pKI | kon (k3) | koff (k4) | t1/2 | Kinetic pKD | cLogDpH7.4 | |
|---|---|---|---|---|---|---|
| ×107 M−1 min−1 | min−1 | min | ||||
| Acetylcholine | 4.55 ± 0.13 | nd | nd | nd | nd | |
| Methacholine | 4.80 ± 0.29 | nd | nd | nd | nd | |
| 4-DAMP | 8.55 ± 0.07 | 9.36 ± 3.88 | 0.29 ± 0.05 | 2.89 ± 0.38 | 8.51 ± 0.03 | −0.70 |
| Atropine | 9.18 ± 0.06 | 21.2 ± 4.77 | 0.07 ± 0.05 | 12.7 ± 7.36 | 9.46 ± 0.21 | −0.41 |
| Glycopyrrolate | 9.43 ± 0.23 | 4.97 ± 0.40 | 0.01 ± 0.00 | 72.9 ± 4.43 | 9.70 ± 0.05 | −1.41 |
| Himbacine | 6.92 ± 0.11 | 0.21 ± 0.20 | 0.47 ± 0.54 | 1.52 ± 0.83 | 6.65 ± 0.06 | 2.90 |
| Ipratropium | 9.13 ± 0.06 | 17.9 ± 6.38 | 0.06 ± 0.05 | 50.7 ± 37.8 | 9.46 ± 0.41 | −1.82 |
| NMS | 9.21 ± 0.07 | 20.9 ± 6.26 | 0.05 ± 0.02 | 35.0 ± 35.0 | 9.63 ± 0.31 | −3.27 |
| Pirenzepine | 6.94 ± 0.09 | 0.03 ± 0.00 | 0.04 ± 0.02 | 19.0 ± 9.52 | 6.88 ± 0.37 | 0.56 |
| QNB | 9.41 ± 0.12 | 2.46 ± 0.69 | 0.008 ± 0.000 | 97.9 ± 2.21 | 9.49 ± 0.13 | 1.70 |
| Tiotropium | 10.05 ± 0.16 | 8.37 ± 1.71 | 0.006 ± 0.001 | 129 ± 29.7 | 10.13 ± 0.10 | −1.75 |
nd, not determined; QNB, quinuclidinyl benzylate.