TABLE 2.
Inhibition of binding of the radioligands labeling opioid receptor subtypes
Values are Ki values except as indicated for displacement of the listed radioligands. Values in parentheses are 95% CIs. Values listed from previous studies were also added as reference. EC50 and Emax values from curve-fitting analyses of these data are shown in Fig. 1.
| Compound | µ Ki (95% CIs) nM | δ Ki (95% CIs) nM | κ Ki (95% CIs) nM | κ/µ | δ/µ | δ/κ |
|---|---|---|---|---|---|---|
| Buprenorphine | 0.903 (0.71–1.21) | 1.51 (0.975–2.35) | 1.29 (0.980–2.09) | 1.43 | 1.67 | 1.17 |
| DADLE | 3.29 (1.96–6.77) | 0.426 (0.272–0.580)a | 3050 (2020–4650) | 927 | 0.129 | 0.000140 |
| DAMGO | 4.15a (1.85–13.1) | 880 (442–1930) | 1200 (556–2770) | 289 | 212 | 0.733 |
| Fentanyl | 7.96 (6.19–10.3) | 539 (300–987) | 202 (128–349) | 25.4 | 67.7 | 2.66 |
| 7-Hydroxymitragynine | 77.9 (45.8–152) | 243 (168–355) | 220 (162–302) | 2.82 | 3.12 | 1.15 |
| 37 (S.E.M.: 4, mouse)b | 91 (S.E.M.: 8, mouse)b | 132 (S.E.M.: 7, mouse)b | 3.57 (mouse)b | 2.46 (mouse)b | 0.69 (mouse)b | |
| 47 (S.E.M.: 18, human)c | 219 (S.E.M.: 41, human)c | 188 (S.E.M.: 38, human)c | 4 (human)c | 4.66 (human)c | 1.16 (human)c | |
| 7.16 (S.E.M.: 0.94, human)d | 236 (S.E.M.: 6, human)d | 74.1 (S.E.M.: 7.8, human)d | 10.4 (human)d | 33.0 (human)d | 3.2 (human)d | |
| 70 (human)e | 470 (human)e | 320 (human)e | 4.57 (human)e | 6.71 (human)e | 1.47 (human)e | |
| Mitragynine | 709 (451–1130) | 6800 (2980–15,900) | 1700 (1090–2710) | 2.40 | 9.60 | 4.00 |
| 230 (S.E.M.: 47, mouse)b | 1010 (S.E.M.: 50, mouse)b | 231 (S.E.M.: 21, mouse)b | 1.00 (mouse)b | 4.39 (mouse)b | 4.37 (mouse)b | |
| 233 (S.E.M.: 48, human)c | >10,000 (human)c | 772 (S.E.M.: 207, human)c | 3.31c (mouse) | Not determined (human)c | Not determined (human)c | |
| 502 (S.E.M.: 19.4, rat)f | 7910 (S.E.M.: 1,140, rat)f | 1200 (S.E.M.: 79.7, rat)f | 2.39 (human)c | 15.8 (rat)c | 6.59 (rat)c | |
| 7.24 (S.E.M.: 3.44, guinea pig)g | 60.3 (S.E.M.: 23.1, guinea pig)g | 1100 (S.E.M.: 436, guinea pig)g | 152 (guinea pig)f | 8.33 (guinea pig)f | 0.0548 (guinea pig)f | |
| 740 (human)e | 6500 (human)e | 1300 (human)e | 1.76 (human)e | 8.78 (human)e | 5 (human)e | |
| Morphine | 4.19 (2.03–11.1) | 250 (177–346) | 40.4 (23.7–70.9) | 9.64 | 59.6 | 6.19 |
| Nalbuphine | 11.0 (9.11–13.3) | 146 (88.3–242) | 13.0 (10.6–16.1) | 1.18 | 13.2 | 11.2 |
| Naltrexone | 1.84 (1.14–3.03) | 37.2 (26.3–53.0) | 1.19 (0.803–1.79) | 0.65 | 20.2 | 31.3 |
| SNC 80 | 2760 (1190–6930) | 34.6 (26.5–45.5) | 2020 (1050–3950) | 0.73 | 0.013 | 0.018 |
| U69,593 | 3180 (1050–11,600) | 6700 (2160–28,000) | 1.62a (1.02–2.64) | 0.0005 | 2.11 | 4140 |
Kd values obtained by homologous competition experiments.
[125I]BNtxA for all three opioid receptor subtypes was used in CHO cells expressing mouse opioid receptors (Váradi et al., 2016).
[125I]BNtxA for all three opioid receptor subtypes was used in CHO cells expressing human opioid receptors (Kruegel et al., 2016).
The same radioligands as the present study were used, but the cell lines used were human HEK-293 cells for MOR and rat basophilic leukemia cells for other receptor subtypes (Obeng et al., 2020).
[3H]DAMGO; [3H]U69,593; and [3H]DADLE were used in HEK-293 cells expressing human µ-, κ-, and δ-opioid receptors, respectively (Ellis et al., 2020).
[3H]DAMGO; [3H]U69,593; and [3H]DADLE were used in rat whole brain tissue excluding the cerebellum (Yue et al., 2018).
[3H]DAMGO; [3H]U69,593; and [3H]DPDPE were used in guinea pig whole brain tissue excluding the cerebellum (Takayama et al., 2002).