TABLE 1.
Pharmacological characterization of kratom derivatives at the µ, δ, and κ opioid receptors.
| Compounds | Binding | cAMP | β-arrestin-2 | ||||
|---|---|---|---|---|---|---|---|
| µOR | pKi | Ki (µM) | pIC50 | IC50 (µM) | α | pEC50 | α |
| DAMGO | 9.6 ± 0.1 (1) | 0.00024 | 8.0 ± 0.1 (6) | 0.0099 | 100 | 6.6 ± 0.1 (6) | 100 |
| SPECIO | 7.1 ± 0.1 (3) | 0.086 | 6.4 ± 0.2 (5) | 0.43 | 38 ± 3 | ND (4) | ND |
| SPG PI | 7.1 ± 0.1 (3) | 0.077 | 6.6 ± 0.2 (5) | 0.23 | 58 ± 4 | ND (4) | ND |
| 7OH SPG | 7.7 ± 0.1 (3) | 0.021 | 6.2 ± 0.2 (6) | 0.61 | 66 ± 6 | ND (4) | ND |
| 7OH PAYN | 5.2 ± 0.1 (3) | 6.15 | 4.7 ± 0.5 (5) | 21.8 | 80 ± 40 | ND (3) | ND |
| PAYN PI | 6.2 ± 0.1 (3) | 0.68 | 5.3 ± 0.2 (4) | 4.82 | 60 ± 6 | ND (3) | ND |
| δOR | pKi | Ki (µM) | pIC50 | IC50 (µM) | α | pEC50 | α |
| Leu-Enk | 9.2 ± 0.1 (3) | 0.00070 | 8.4 ± 0.1 (9) | 0.0042 | 100 | 7.4 ± 0.1 (7) | 100 |
| SPECIO | 5.4 ± 0.1 (3) | 4.34 | ND (3) | ND | ND | ND (5) | ND |
| SPG PI | 6.0 ± 0.1 (3) | 0.94 | 5.1 ± 0.3 (4) | 8.53 | 80 ± 20 | ND (4) | ND |
| 7OH SPG | 6.3 ± 0.1 (3) | 0.46 | 5.6 ± 0.1 (6) | 2.27 | 76 ± 6 | ND (4) | ND |
| 7OH PAYN | 4.9 ± 0.2 (4) | 12.7 | 5.2 ± 0.3 (5) | 5.74 | 70 ± 20 | ND (3) | ND |
| PAYN PI | 6.0 ± 0.1 (3) | 0.92 | ND (5) | ND | ND | ND (3) | ND |
| κOR | pKi | Ki (µM) | pIC50 | IC50 (µM) | α | pEC50 | α |
| U50,488 | 10.0 ± 0.2 (2) | 0.000099 | 8.5 ± 0.1 (5) | 0.0034 | 100 | 7.1 ± 0.1 (6) | 100 |
| SPECIO | 6.2 ± 0.1 (4) | 0.59 | 5.6 ± 0.2 (4) | 2.50 | 60 ± 7 | ND (5) | ND |
| SPG PI | 6.1 ± 0.1 (3) | 0.75 | 4.7 ± 0.5 (4) | 20.6 | 80 ± 30 | ND (3) | ND |
| 7OH SPG | 5.8 ± 0.2 (3) | 1.63 | 5.1 ± 0.3 (3) | 7.71 | 80 ± 20 | ND (5) | ND |
| 7OH PAYN | 5.1 ± 0.1 (3) | 7.46 | ND (3) | ND | ND | ND (3) | ND |
| PAYN PI | 5.9 ± 0.1 (4) | 1.31 | ND (3) | ND | ND | ND (3) | ND |
Affinity (pKi, drug concentration at which 50% of receptors is occupied). cAMP inhibition potencies (pIC50, drug concentration at 50% maximal efficacy) and efficacies (α, % inhibition at maximal efficacy normalized to DAMGO [µOR], Leu-enkephalin [δOR], or U50,488 [κOR]) of OR agonists to inhibit cAMP production are indicated ± SEM. β-arrestin-2 recruitment potencies (pEC50) and efficacies (α, normalized to DAMGO, Leu-enkephalin or U50,488) of OR agonists to recruit β-arrestin 2 are indicated ± SEM. The number of repetitions for each drug is indicated in parentheses. ND, not detectable. Data for 7-hydroxymitragynine, speciogynine, and paynantheine in the GloSensor cAMP assay and PathHunter β-arrestin-2 recruitment assay was generated in a previous publication (Gutridge et al., 2020) and is shown in Supplemental Table S1 for easy comparison to the kratom derivatives.