EC50 and Emax values for BUP and SAM alone and in combination in stimulating the activation of Gαi2-Kir, GαoA-Kir, and β-arrestin recruitment mediated by the MOR, KOR, and DOR
EC50 values are expressed in total molarity when buprenorphine and samidorphan were combined. Data are the mean values ± S.E.M. from six determinations.
| Gαi2-Kir | GαoA-Kir | β-Arrestin-GRK2 | ||||
|---|---|---|---|---|---|---|
| EC50 | Emax | EC50 | Emax | EC50 | Emax | |
| nM | % | nM | % | nM | % | |
| MOR | ||||||
| DAMGO | 30.0 ± 7.0 | 100 | 24 ± 1.0 | 100 | 32 ± 1.0 | 100 |
| Morphine | 142 ± 32 | 92 ± 2.0 | 89 ± 17 | 90 ± 4.0 | 71 ± 4.5 | 84 ± 2.0 |
| BUP | 0.40 ± 0.10 | 27 ± 0.70 | 0.30 ± 0.020 | 30 ± 0.020 | 0.40 ± 0.020 | 33 ± 3.5 |
| SAM | No activity | NA | No activity | NA | No activity | NA |
| 1:3 BUP/SAM | >10,000 | ∼20 | >100 | ∼15 | No activity | NA |
| KOR | ||||||
| U50,488 | 3.6 ± 0.070 | 100 | 6.4 ± 1.1 | 100 | 58 ± 51 | 100 |
| Morphine | 960 ± 110 | 55 ± 9.0 | >1000 | ∼50 | >1000 | ∼50 |
| BUP | 0.80 ± 0.10 | 14 ± 4.0 | NA | ∼7 | NA | ∼15 |
| SAM | 2.5 ± 0.20 | 32 ± 4.0 | 5.0 ± 1.0 | 21 ± 2.0 | NA | ∼12 |
| 1:3 BUP/SAM | 0.60 ± 0.20 | 14 ± 3.0 | NA | ∼7 | NA | ∼13 |
| DOR | ||||||
| SNC-80 | 1.2 ± 0.40 | 100 | 1.0 ± 0.30 | 100 | 6.2 ± 2.1 | 100 |
| Morphine | >10,000 | ∼40 | >10,000 | ∼50 | >10,000 | ∼25 |
| BUP | 0.80 ± 0.10 | 56 ± 4.0 | 0.70 ± 0.020 | 37 ± 2.0 | 1.8 ± 1.0 | 16 ± 5.0 |
| SAM | NA | ∼10 | NA | ∼10 | NA | ∼12 |
| 1:3 BUP/SAM | 1.9 ± 1.3 | 20 ± 2.0 | 2.9 ± 0.10 | 31 ± 1.0 | 6.8 ± 2.0 | 14 ± 5.0 |
NA, not applicable.