Table 1.
MOR affinities, G protein dissociation BRET, and β-arrestin2 recruitment potency and efficacy
| Compound | [3H]-DAMGO Binding |
G protein (GoA) dissociation |
β-Arrestin2 recruitment |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ki nM (pKi ±SEM) | EC50 (nM) | pEC50 ± SEM | Emax (% DAMGO) | Log (Emax/EC50) | ΔLog (Emax/EC50) | ΔΔLog (Emax/EC50) | Bias Factor (for G protein) | EC50 (nM) | pEC50 ± SEM | Emax (% DAMGO) | Log (Emax/EC50) | ΔLog (Emax/EC50) | ΔΔLog (Emax/EC50) | Bias Factor (for β-arr) | |
| DAMGO | 4.37∗ (8.36 ± 0.07) | 12.03 | 7.92 ± 0.06 | 100.0 | 7.92 | 0 | 0 | 1 | 18.7 | 7.73 ± 0.03 | 100.0 | 7.73 | 0 | 0 | 1 |
| Isotonitazene | 0.490 (9.31 ± 0.14) | 0.107 | 9.97 ± 0.09 | 118.8 ± 2.3 ∗∗ | 10.05 | 2.13 | 0.59 | 3.85 | 0.705 | 9.15 ± 0.06 | 132.4 ± 2.5 ∗∗ | 9.27 | 1.54 | −0.60 | 0.26 |
| Fentanyl | 6.03 (8.22 ± 0.13) | 9.21 | 8.03 ± 0.09 | 112.2 ± 2.7 ∗∗ | 8.10 | 0.18 | 0.53 | 3.38 | 38.7 | 7.41 ± 0.04 | 92.0 ± 1.5 ∗∗ | 7.38 | −0.35 | −0.53 | 0.29 |
| N-desethyl isotonitazene | 0.741 (9.13 ± 0.22) | 0.252 | 9.60 ± 0.12 | 114.5 ± 3.6 ∗∗ | 9.66 | 1.74 | 0.67 | 4.66 | 2.01 | 8.70 ± 0.05 | 127.0 ± 1.9 ∗∗ | 8.80 | 1.07 | −0.67 | 0.21 |
| Metonitazene | 0.776 (9.11 ± 0.11) | 1.74 | 8.76 ± 0.10 | 107.4 ± 3.1 ∗∗ | 8.78 | 0.86 | 0.15 | 1.41 | 3.83 | 8.42 ± 0.05 | 104.4 ± 1.5 | 8.44 | 0.71 | −0.15 | 0.71 |
| Morphine | 2.63 (8.58 ± 0.17) | 50.2 | 7.30 ± 0.09 | 98.94. ± 3.9 | 7.23 | −0.68 | 0.22 | 1.65 | 74.7 | 7.13 ± 0.09 | 50.8 ± 2.0 ∗∗ | 6.83 | −0.90 | −0.22 | 0.60 |
MOR affinities for compounds in this study were determined using [3H]-DAMGO competition binding. G protein (GoA) dissociation and β-arrestin2 recruitment activities were determined by BRET in HEK293T cells. All data represent average and standard error of the mean (S.E.M) from at least three independent experiments performed in duplicate, and are represented as mean ± SEM. ∗The [3H]-DAMGO binding value shown for DAMGO is the pKd ±SEM. Emax values marked with ∗∗ are statistically significantly different from that of DAMGO as determined by the extra sum-of-squares F test, with p < 0.0001.