Inhibition constants of selective muscarinic ligands for wild-type M2 and M3, and hybrid M3 (o2M2) and M3(o3M2) receptors
Negative logarithms of inhibition constants (pKi) were obtained by nonlinear regression of data from competition experiments of antagonist versus [3H]NMS. Equation 2 was fitted to the data to obtain IC50. Ki was computed according eq. 3. Data are means ± S.E.M. from four independent experiments.
| M2 | M3 | M3(o2M2) | M3(o3M2) | |
|---|---|---|---|---|
| 4-DAMP | 7.72 ± 0.06 | 8.50 ± 0.09 | 6.84 ± 0.05* | 8.35 ± 0.07 |
| AF-DX 116 | 7.18 ± 0.04 | 5.68 ± 0.05 | 5.54 ± 0.05 | 5.68 ± 0.06 |
| Himbacine | 7.56 ± 0.08 | 6.93 ± 0.03 | 6.83 ± 0.08 | 6.91 ± 0.06 |
| Methoctramine | 7.29 ± 0.04 | 5.69 ± 0.12 | 5.89 ± 0.11 | 7.17 ± 0.04* |
↵* Significantly different from wild-type M3 (P < 0.01 by Student's two-tailed t test).