Pharmacological characterization of AC-42 and other muscarinic agonists on M1 to M5. Assays were carried out using R-SAT. Values represent the mean ± S.E.M. Maximum response (Max. Resp.) values are normalized relative to the maximum response of the cells to carbachol.
| M1 | M2 | M3 | M4 | M5 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Max. Resp. | pEC50 | N | Max. Resp. | pEC50 | N | Max. Resp. | pEC50 | N | Max. Resp. | pEC50 | N | Max. Resp. | pEC50 | N | |
| % | % | % | % | % | |||||||||||
| AC-42 | 66 ± 3 | 6.54 ± 0.05 | 32 | N.R. | 6 | N.R. | 15 | N.R. | 13 | N.R. | 13 | ||||
| Carbachol | 100 | 6.13 ± 0.03 | 47 | 100 | 6.34 ± 0.09 | 19 | 100 | 6.55 ± 0.05 | 26 | 100 | 6.54 ± 0.05 | 20 | 100 | 6.64 ± 0.14 | 18 |
| Pilocarpine | 94 ± 2 | 5.67 ± 0.04 | 32 | 70 ± 8 | 5.56 ± 0.18 | 7 | 59 ± 9 | 5.79 ± 0.08 | 15 | 66 ± 7 | 5.35 ± 0.09 | 10 | 77 ± 7 | 5.60 ± 0.11 | 12 |
| McN-A-343 | 96 ± 4 | 6.23 ± 0.08 | 6 | 98 ± 11 | 4.94 ± 0.08 | 4 | 50 ± 6 | 5.45 ± 0.05 | 4 | 102 ± 12 | 6.25 ± 0.12 | 5 | 119 ± 15 | 6.07 ± 0.11 | 4 |
| Oxotremorine-M | 106 ± 5 | 7.41 ± 0.12 | 8 | 108 ± 4 | 6.28 ± 0.40 | 2 | 119 ± 21 | 7.04 ± 0.25 | 3 | 125 ± 3 | 7.51 ± 0.24 | 4 | 117 ± 21 | 7.07 ± 0.28 | 3 |
| CI-1017 | 76 ± 4 | 6.34 ± 0.06 | 6 | 99 ± 13 | 5.46 ± 0.21 | 5 | 51 ± 6 | 5.85 ± 0.09 | 9 | 118 ± 10 | 6.40 ± 0.08 | 8 | 62 ± 9 | 5.97 ± 0.12 | 8 |
| WAY-132983-A5 | 107 ± 8 | 8.34 ± 0.16 | 8 | 73 ± 1 | 7.44 ± 0.17 | 4 | 52 ± 3 | 7.96 ± 0.15 | 11 | 121 ± 4 | 9.01 ± 0.07 | 3 | 59 ± 12 | 8.18 ± 0.22 | 6 |
| Xanomeline | 122 ± 6 | 7.19 ± 0.09 | 16 | 108 ± 10 | 6.25 ± 0.26 | 6 | 66 ± 6 | 6.63 ± 0.21 | 8 | 112 ± 10 | 7.56 ± 0.12 | 4 | 95 ± 11 | 6.60 ± 0.28 | 4 |
pEC50, −log (EC50); N.R., no response; maximum response of AC-42 was not significantly different from zero on the M2 to M5 receptor subtypes.