Table 1.
Inhibitory constant values (Ki ± S.E.M.) and selectivity ratios of codeine-6-O-sulfate (C6SU) and 14-methoxycodeine-6-O-sulfate (14-OMeC6SU) compared to codeine in competition binding assays with [3H]DAMGO, [3H]IleDelt II and [3H]U-69593, which are μ type opioid receptor (MOR), δ type opioid receptor (DOR) and κ type opioid receptor (KOR) specific radioligands, respectively performed in rat or guinea pig brain membrane homogenates. The unlabeled form of the radioligands are also indicated for control and for further comparison.
| Ki ± S.E.M. (nM) | Selectivity Ratio | |||||
|---|---|---|---|---|---|---|
| Compounds | [3H]DAMGO (μ) 1 | [3H]IleDelt II (δ) 1 | [3H]U-69593 (κ) 2 | δ/μ | κ/μ | δ/κ |
| 14-OMeC6SU | 3.37 ± 0.48 ** (n = 6) |
345.52 ± 132.52 (n = 5) |
245.57 ± 215.01 (n = 5) |
102.5 | 72.9 | 1.4 |
| C6SU | 96.91 ± 20.3 * (n = 5) |
968.28 ± 471.38 (n = 6) |
N.D.3 (n = 5) |
9.9 | - | - |
| Codeine | 736.74 ± 319.63 (n = 4) |
N.D. 4 (n = 4) |
N.D. 4 (n = 4) |
- | - | - |
| Morphine 5 | 0.76 ± 0.08 (n = 7) |
114.21 ± 44.83 (n = 6) |
N.D. 4 (n = 4) |
150.3 | - | - |
| Homologous ligand6 | 0.59 ± 0.12 (n = 5) |
3.81 ± 0.88 (n = 6) |
5.51 ± 0.97 (n = 5) |
- | - | - |
1 performed in rat brain membrane homogenates; 2 performed in guinea pig brain membrane homogenates; 3 the compound did not inhibit total specific radioligand binding (100%) to 50%, thus the Ki value cannot be interpreted (N.D. not determined); 4 the compound did not alter significantly (One-sample t test) the total specific radioligand binding (100%), thus the Ki value cannot be interpreted (N.D. not determined); 5 adopted from [23]; 6 indicates the unlabeled form of the radioligands and represent a control for the assay (μ: DAMGO δ: IleDelt II, κ: U-69593); * compared to codeine (One-way ANOVA, with Sidak’s multiple comparison test; ** P < 0.01, *** P < 0.001).