Table 1. MR Affinities (pKi Values) of Monomeric Reference Compounds 22, 31, and 35, Homodimeric Ligands 25, 27–29, 54, 58, and 59, as well as Heterodimeric Ligands 34, 38, 39, 43, 44, 46, 48, 50–52, 60, 61, 63, 64, 66, 67, 69, 70, and 72 Obtained from Equilibrium Competition-Binding Studies with [3H]5 at Live CHO-hMxR Cells (x = 1–5).
| M1R |
M2R |
M3R |
M4R |
M5R |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Cmpd. | pKi | slopea | pKi | slopea | pKi | slopea | pKi | slopea | pKi | slopea |
| 22 | n.d. | n.d. | 4.90 ± 0.16 | –1.01 ± 0.10 | n.d. | n.d. | n.d. | n.d. | n.d. | n.d |
| 25 | 7.36 ± 0.10 | –1.04 ± 0.07 | 7.75 ± 0.18 | –0.92 ± 0.18 | 7.30 ± 0.02 | –0.95 ± 0.04 | n.d. | n.d. | n.d. | n.d. |
| 27 | 8.30 ± 0.08 | –0.89 ± 0.10 | 8.46 ± 0.17 | –0.94 ± 0.08 | 8.14 ± 0.04 | –1.14 ± 0.03 | n.d. | n.d. | n.d. | n.d. |
| 28 | 8.41 ± 0.05 | –1.30 ± 0.05 | 8.67 ± 0.11 | –0.84 ± 0.07 | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. |
| 29 | 7.72 ± 0.13 | –1.15 ± 0.18 | 8.38 ± 0.13 | –0.83 ± 0.06 | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. |
| 31 | n.d. | n.d. | 5.88 ± 0.29 | –0.87 ± 0.05 | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. |
| 34 | 8.57 ± 0.05 | –1.13 ± 0.05 | 9.12 ± 0.05 | –1.43 ± 0.20 | 7.01 ± 0.11 | –1.12 ± 0.07 | 7.95 ± 0.50 | –1.18 ± 0.06 | 7.09 ± 0.07 | –1.09 ± 0.20 |
| 35 | 7.26 ± 0.10 | 0.92 ± 0.08 | 8.67 ± 0.03 | –0.87 ± 0.09 | 6.25 ± 0.06 | –0.93 ± 0.20 | 8.00 ± 0.01 | –0.77 ± 0.02b | 6.86 ± 0.17 | –1.09 ± 0.15 |
| 38 | 8.47 ± 0.08 | –1.03 ± 0.12 | 8.82 ± 0.14 | –1.08 ± 0.22 | 8.12 ± 0.05 | –1.36 ± 0.09 | 7.99 ± 0.28 | –0.98 ± 0.12 | 8.47 ± 0.06 | –1.17 ± 0.10 |
| 39 | 7.62 ± 0.19 | –1.40 ± 0.30 | 8.37 ± 0.28 | –1.51 ± 0.26 | 7.01 ± 0.10 | –0.85 ± 0.04 | 7.52 ± 0.35 | –1.25 ± 0.10 | 7.03 ± 0.03 | –1.09 ± 0.18 |
| 43 | 8.35 ± 0.07 | –1.47 ± 0.17 | 9.30 ± 0.05 | –2.19 ± 0.06b | 7.21 ± 0.04 | –1.34 ± 0.16 | n.d. | n.d. | n.d. | n.d. |
| 44 | 8.39 ± 0.03 | –1.05 ± 0.05 | 9.34 ± 0.03 | –1.14 ± 0.07 | 6.84 ± 0.03 | –0.93 ± 0.04 | 8.24 ± 0.08 | –0.94 ± 0.06 | 7.00 ± 0.09 | –1.21 ± 0.19 |
| 46 | 8.84 ± 0.11 | –1.45 ± 0.02b | 10.14 ± 0.11 | –0.96 ± 0.05 | 7.88 ± 0.06 | –1.17 ± 0.08 | 8.59 ± 0.05 | –1.17 ± 0.04 | 7.47 ± 0.03 | –1.07 ± 0.22 |
| 48 | 7.68 ± 0.12 | –1.03 ± 0.22 | 8.66 ± 0.03 | –1.24 ± 0.22 | 7.46 ± 0.12 | –1.35 ± 0.06b | 8.07 ± 0.19 | –1.17 ± 0.11 | 7.27 ± 0.05 | –1.11 ± 0.10 |
| 50 | 8.40 ± 0.08 | –1.00 ± 0.05 | 9.24 ± 0.11 | –1.38 ± 0.22 | 6.86 ± 0.04 | –1.05 ± 0.09 | 8.48 ± 0.03 | –1.4 ± 0.06 | 7.03 ± 0.07 | –1.01 ± 0.25 |
| 51 | 8.37 ± 0.03 | –1.47 ± 0.05b | 9.16 ± 0.07 | –1.86 ± 0.05b | 7.23 ± 0.06 | –1.05 ± 0.10 | n.d. | n.d. | n.d. | n.d. |
| 52 | 7.78 ± 0.08 | –1.82 ± 0.19b | 9.11 ± 0.10 | –1.12 ± 0.15 | 6.23 ± 0.10 | –1.01 ± 0.03 | 8.10 ± 0.11 | –0.85 ± 0.07 | 6.88 ± 0.10 | –1.31 ± 0.10 |
| 54 | 6.59 ± 0.07 | –1.14 ± 0.12 | 6.05 ± 0.06 | –1.33 ± 0.18 | 5.64 ± 0.09 | –1.05 ± 0.34 | 5.63 ± 0.04 | –1.00 ± 0.06 | 5.87 ± 0.25 | –1.35 ± 0.20 |
| 58 | 8.69 ± 0.09 | –2.06 ± 0.19b | 9.83 ± 0.07 | –1.53 ± 0.15 | 7.78 ± 0.05 | –1.27 ± 0.10 | n.d. | n.d. | n.d. | n.d. |
| 59 | 8.53 ± 0.08 | –1.75 ± 0.34 | 9.24 ± 0.06 | –1.31 ± 0.09 | 7.89 ± 0.07 | –1.22 ± 0.09 | n.d. | n.d. | n.d. | n.d. |
| 60 | 8.80 ± 0.10 | –1.32 ± 0.31 | 9.65 ± 0.15 | –1.79 ± 0.09b | 7.76 ± 0.14 | –1.28 ± 0.04b | n.d. | n.d. | n.d. | n.d. |
| 61 | 8.88 ± 0.08 | –1.61 ± 0.03b | 9.47 ± 0.07 | –2.37 ± 0.15b | 7.87 ± 0.02 | –0.99 ± 0.04 | 8.87 ± 0.08 | –1.14 ± 0.11 | 8.37 ± 0.24 | –1.02 ± 0.11 |
| 63 | 8.79 ± 0.09 | –1.19 ± 0.07 | 9.71 ± 0.08 | –1.37 ± 0.14 | 7.77 ± 0.03 | –1.22 ± 0.05 | n.d. | n.d. | n.d. | n.d. |
| 64 | 8.56 ± 0.11 | –1.59 ± 0.15 | 9.44 ± 0.06 | –1.84 ± 0.17b | 7.55 ± 0.04 | –1.40 ± 0.10 | 8.57 ± 0.02 | –1.01 ± 0.04 | 6.96 ± 0.04 | –1.26 ± 0.14 |
| 66 | 8.28 ± 0.05 | –1.32 ± 0.19 | 9.16 ± 0.20 | –1.64 ± 0.23 | 7.20 ± 0.19 | –1.33 ± 0.08 | n.d. | n.d. | n.d. | n.d. |
| 67 | 8.38 ± 0.06 | –1.54 ± 0.14 | 8.94 ± 0.07 | –2.14 ± 0.16b | 7.52 ± 0.04 | –1.25 ± 0.09 | 8.50 ± 0.08 | –1.52 ± 0.26 | 7.62 ± 0.06 | –1.51 ± 0.12 |
| 69 | 8.42 ± 0.19 | –1.74 ± 0.19 | 9.17 ± 0.18 | –1.52 ± 0.31 | 7.26 ± 0.22 | –1.23 ± 0.12 | n.d. | n.d. | n.d. | n.d. |
| 70 | 8.51 ± 0.13 | –1.10 ± 0.07 | 8.96 ± 0.08 | –2.14 ± 0.18b | 7.72 ± 0.06 | –1.21 ± 0.13 | 8.29 ± 0.02 | –1.41 ± 0.05b | 7.37 ± 0.08 | –1.01 ± 0.12 |
| 72 | 8.52 ± 0.09 | –1.66 ± 0.20 | 9.63 ± 0.03 | –1.31 ± 0.13 | 7.88 ± 0.03 | –1.42 ± 0.09b | 8.39 ± 0.09 | –1.50 ± 0.17 | 7.69 ± 0.33 | –0.85 ± 0.07 |
a
Curve slope of the four-parameter logistic fit. Presented are mean values ± SEM from three to five independent experiments (each performed in triplicate). Kd values reported previously22/applied concentrations of [3H]5: M1: 0.12/0.2 nM; M2: 0.090/0.2 nM; M3: 0.0895/0.2 nM; M4: 0.040/0.1 nM; and M5: 0.24/0.3 nM.
b
Slope different from unity (P < 0.05).