Binding affinities of oxotremorine, CMI-936, and CMI-1145 for the M2 and M4 mAChRs
| KiValues | Ki-M2/Ki-M4 | ||
|---|---|---|---|
| M2 | M4 | ||
| μM | |||
| Oxotremorine | 0.32 ± 0.08 | 0.51 ± 0.18 | 0.63 |
| CMI-936 | 10.1 ± 1.4 | 0.65 ± 0.102-150 | 15.5 |
| CMI-1145 | 5.2 ± 3.1 | 0.80 ± 0.082-150 | 6.5 |
Binding affinities (K i values) were determined in [3H]NMS competition binding assays as described underMaterials and Methods, using membranes prepared from CHO-K1 cell lines stably expressing the human M2 or M4 mAChRs (Dörje et al., 1991). [3H]NMS was used at a concentration of 50 pM. [3H]NMS saturation binding studies yielded the following [3H]NMS affinities (K d values): M2, 545 ± 82 pM; M4, 160 ± 6 pM (means ± S.D.; n = 3). IC50 values were converted to K i values by using the Cheng-Prusoff equation (Cheng and Prusoff, 1973). Data are presented as means ± S.D. from two or three separate experiments carried out in duplicate.
↵2-150 Significantly different from the corresponding M2 receptor value (p < 0.05, ttest).