Reported bias of μ-opioid agonists from a range of published studies
Reported bias along with bias factor. For clarity, with regard to G protein signaling, only data calculated from G protein-activation assays or cAMP signaling are included.
| Ligand | Bias | Bias Factor | Bias Quantification | Assays (receptor species) | Reference Ligand | Reference |
|---|---|---|---|---|---|---|
| Buprenorphine | G protein | 69 | ∆∆log(τ/KA) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Morphine | Burgueno et al., 2017 |
| DynA 1-6 | G protein | 4.6 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | (Thompson et al., 2015b) |
| Endomorphin-1 | Arrestin; G protein | 0.06; 35.6 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.); cAMP (hMOPr) vs. Arrestin-2 recruitment (N.R.) | DAMGO | (Thompson et al., 2015b) |
| Arrestin | N.R. | Correlation of operational efficacy (τ) | GTPγS (rMOPr) vs. Arrestin-3 recruitment (N.R.) | N.A. | McPherson et al., 2010 | |
| Arrestin | N.R. | ∆∆log(τ/KA) | Gαi3 BRET (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | Thompson et al., 2016 | |
| Endomorphin-2 | Arrestin | N.R. | (βlig) | GTPγS (rMOPr) vs. Arrestin-3 recruitment (N.R) | Leu-enkephalin | Rivero et al., 2012 |
| Arrestin | N.R. | Correlation of operational efficacy (τ) | GTPγS (rMOPr) vs. Arrestin-3 recruitment (N.R.) | N.A. | McPherson et al., 2010 | |
| Arrestin | 0.23 | ∆∆log(τ) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Morphine | Burgueno et al., 2017 | |
| G protein | N.R. | ∆∆log(τ/KA) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Pfizer standard 1 | (Hothersall et al., 2017) | |
| Fentanyl | Arrestin; G protein | 0.18; 2.8 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| Arrestin | 0.05; 0.15 | ∆∆log(τ/KA) | GTPγS (mMoPr) v Arrestin-3 recruitment (mMoPr); GTPγS (mMOPr (brain)) v Arrestin-3 recruitment (mMOPRr) | DAMGO | (Schmid et al., 2017) | |
| G protein | 9.1 | ∆∆log(τ/KA) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Morphine | Burgueno et al., 2017 | |
| Arrestin | 0.37 | ∆∆log(τ) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Morphine | Burgueno et al., 2017 | |
| Loperamide | G protein | 10.1; 9.4 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.); cAMP (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | (Thompson et al., 2015b) |
| G protein | 18.3; 17.0 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-2 recruitment (N.R); cAMP (hMOPr) vs. Arrestin-2 recruitment (N.R.) | DAMGO | (Thompson et al., 2015b) | |
| Met-enkephalin | G protein | N.R. | ∆∆log(τ/KA) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Pfizer standard 1 | (Hothersall et al., 2017) |
| Morphine | Arrestin | 0.1 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | (Thompson et al., 2015b) |
| Arrestin | N.R. | ∆∆log(τ/KA) | Gαi1 BRET (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | Thompson et al., 2016 | |
| G protein; Arrestin | 1.3; 0.62 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) | |
| G protein | 1.9 | ∆∆log(τ/KA) | GTPγS (mMOPR (brain)) v Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| Sufentanil | Arrestin | 0.16 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| Arrestin | 0.06; 0.14 | ∆∆log(τ/KA) | GTPγS (mMOPr) v Arrestin-3 recruitment (mMOPR); GTPγS (mMOPr (brain)) v Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| α-Neo | G protein | 14.6 | ∆∆log(τ/KA) | cAMP (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | (Thompson et al., 2015b) |
| G protein | 8 | ∆∆log(τ/KA) | cAMP (hMOPr) vs. Arrestin-2 recruitment (N.R) | DAMGO | (Thompson et al., 2015b) | |
| G protein | N.R. | ∆∆log(τ/KA) | Gαi2 BRET (hMOPr) vs. Arrestin-3 recruitment (N.R.) | DAMGO | Thompson et al., 2016 | |
| PZM 21 | G protein | N.R. | ∆∆log(τ/KA) | cAMP vs. Arrestin-3 recruitment | N.R. | Manglik et al., 2016 |
| TRV 130 | G protein | 3 | RAi | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Morphine | Dewire et al., 2013 |
| G protein | 4.2 | ∆∆log(τ) | cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | Morphine | Burgueno et al., 2017 | |
| SR-15098a | G protein | 29; 19 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| G protein | 11; 55 | ∆∆log(τ/KA) | GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| SR-15099 | G protein | 47; 27 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| G protein | 12; 55 | ∆∆log(τ/KA) | GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| SR-17018 | G protein | 85; 40 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| G protein | 30; 102 | ∆∆log(τ/KA) | GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| (±) SR-11501 | Arrestin | 0.41 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| Arrestin | 0.12; 0.23 | ∆∆log(τ/KA) | GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| (±) SR-14968 | G protein | 36; 5.1 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| G protein | 6.7; 34 | ∆∆log(τ/KA) | GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) | |
| (±) SR-14969a | G protein | 11; 2.5 | ∆∆log(τ/KA) | GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr) | DAMGO | (Schmid et al., 2017) |
| G protein | 2.9; 8.6 | ∆∆log(τ/KA) | GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr) | DAMGO | (Schmid et al., 2017) |
N.A. not applicable; N.R, not reported; RAi, intrinsic relative activity.