Table 1.
Comparison of Binding Affinities at Opioid Receptors of N-Methylmorphinans 1–4 and Their N-Phenethyl Analogues 1a–4a.
| Compound | Ki (nM)a | ||||
|---|---|---|---|---|---|
| µOR | δOR | κOR | Ki ratio δOR/µOR | Ki ratio κOR/µOR | |
| Morphine (1) | 3.35 ± 0.30 | 195 ± 26 | 96.4 ± 0.5 | 58 | 29 |
| 1a | 0.25 ± 0.09*** | 24.5 ± 8.7* | 93.5 ± 2.9 | 98 | 374 |
| Oxymorphone (2) | 1.41 ± 0.30 | 79.1 ± 9.3 | 32.6 ± 9.8 | 56 | 23 |
| 2a | 0.12 ± 0.07* | 10.7 ± 5.1* | 42.2 ± 7.3 | 89 | 352 |
| 14-OMO (3) | 0.27 ± 0.09 | 9.08 ± 0.31 | 10.3 ± 1.8 | 34 | 38 |
| 3a | 0.19 ± 0.02 | 1.81 ± 0.68*** | 15.8 ± 8.8 | 9.5 | 83 |
| 14-MM (4) | 0.25 ± 0.04 | 18.6 ± 0.98 | 12.8 ± 1.5 | 74 | 51 |
| 4a | 0.24 ± 0.03 | 1.45 ± 0.31*** | 35.3 ± 5.5** | 6.0 | 147 |
aDetermined in competition binding assays using membranes from CHO cells stably expressing the human opioid receptors. Values represent the mean ± SEM (n = 3–4). *P < 0.05, **P < 0.01 and ***P < 0.001 for N-methylmorphinans vs. respective N-phenethyl analogues (unpaired t-test).