Table 1. Comparative Binding and Activity Properties of Muscarinic DREADD Ligandsa.
| hMl |
hMIDq |
hM4 |
hM4Di |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| pK1 | pECso IP1 | pEC50 pERK | pK1 | pEC50 IP1 | pEC50 pERK | pK1 | pEC50 pERK | pEC50 cAMP | pK1 | pEC50 pERK | pEC50 cAMP | |
| ACh | 4.96 (±0.09) N = 9 | 7.59 (±0.16) N = 9 | 5.76 (±0.16) N = 12 | 2.83 (±0.07) N = 8 | 3.09 (±0.27) N = 8 | 2.45 (±0.18) N = 7 | 4.82 (±0.15) N = 3 | 7.51 (±0.30) N = 6 | 6.92 (±0.13) N = 4 | 2.66 (±0.11) N = 3 | 2.73 (±0.28) N = 3 | 2.75 (±0.09) N = 4 |
| CNO | 5.10 (±0.03) N = 7 | N/A | N/A | 6.74 (±0.10) N = 9 | 8.61 (±0.03) N = 10 | 7.70 (±0.25) N = 11 | 4.85 (±0.05) N = 3 | N/A | 4.82 (0.43) N = 3 | 6.30 (±0.22) N = 3 | 6.89 (±0.12) N = 3 | 7.29 (±016) N = 4 |
| C21 | 5.97 (±0.05) N = 7 | N/A | N/A | 7.20 (±0.21) N = 8 | 8.91 (±0.01) N = 4 | 6.54 (±0.52) N = 3 | 5.44 (±0.11) N = 3 | N/A | 5.73 (±0.13) N = 3 | 6.75 (±0.26) N = 3 | 7.77 (±0.31) N = 3 | 7.75 (±0.14) N = 4 |
| perlapine | 7.04 (±0.06) N = 7 | N/A | N/A | 7.58 (±0.07) N = 8 | 8.38 (±0.07) N = 7 | 6.80 (±0.19) N = 4 | 6.58 (±0.10) N = 3 | N/A | 7.25 (±0.71) N = 3 | 7.17 (±0.08) N = 3 | 7.27 (±0.33) N = 3 | 7.20 (±0.19) N = 4 |
a
Summary for the binding affinities (pKi) and potency (pEC50) for ACh and CNO at various signal transduction assays of C21 and perlapine at muscarinic DREADDs and wildtype receptors. Data represents the mean ± SEM of at least three independent experiments carried out in duplicate.