Functional parameters, agonistic and PAM activity, and selectivity for M1R of M1 PAMs
Results of the in vitro functional parameters for M1R represent the mean and S.E.M. of three independent experiments.
| Compound | M1R Agonistic Activity pEC50 | PAM Activity Against Muscarinic Receptor Subtypes pIP | ||||||
|---|---|---|---|---|---|---|---|---|
| M1R | M2R | M3R | M4R | M5R | ||||
| Mean | S.E.M. | Mean | S.E.M. | |||||
| BQCA | 6.16 | 0.04 | 7.13 | 0.06 | <5.00 | <5.00 | <5.00 | <5.00 |
| Compound A | 6.17 | 0.10 | 7.39 | 0.08 | <5.00 | <5.00 | <5.00 | <5.00 |
| Compound B | 7.14 | 0.20 | 7.99 | 0.09 | <5.00 | <5.00 | 6.00 | <5.00 |
| Compound C | 8.79 | 0.24 | 8.68 | 0.19 | <5.00 | <5.00 | <5.00 | <5.00 |
| Compound D | 6.66 | 0.19 | 8.07 | 0.11 | <5.00 | <5.00 | <5.00 | <5.00 |
| Compound E | 5.68 | 0.32 | 7.10 | 0.10 | <5.00 | <5.00 | <5.00 | <5.00 |
| Compound F | <5.00 | N/A | 6.56 | 0.19 | <5.00 | <5.00 | <5.00 | <5.00 |
EC50, eliciting 50% of the maximal response of an endogenous ligand, acetylcholine (ACh), reflects the agonistic activity for M1R under conditions without ACh; IP, inflection point (PAM potency for M1-M5R, which is determined from titration of PAM in the presence of a low concentration of acetylcholine (ACh), eliciting 20% of the maximal ACh response; M1R, M1 muscarinic receptor; N/A, not available; PAM, positive allosteric modulator.