Table 2.
Activity of test compounds in β-arrestin assays at human GPR55 and GPR18
| Compd | Human GPR55 | Human GPR18 | |||
|---|---|---|---|---|---|
| EC50 (µM) (% activation) | IC50 (µM) (% inhibition) | EC50 (µM) (% activation) | IC50 (µM) (% inhibition) | ||
| 1 | Δ9-THC | – | 14.2 [52] | 4.61 [52] | – |
| 2 | CP55,940 | – | 1.61 [53] | – | 5.99 [52] |
| 3-Amido-indole and -indazoles (A) | |||||
| 4 | FDU-NNEI | > 10 (13%) | > 10 (2%) | > 10 (20%) | > 10 (− 1%) |
| 5 | MMB-018 | > 10 (5%) | > 10 (5%) | > 10 (13%) | > 10 (− 4%) |
| 6 | AMB | > 10 (15%) | > 10 (28%) | > 10 (42%) (n = 1) | > 10 (15%) |
| 7 | MMB-2201 | > 10 (5%) | > 10 (− 10%) | > 10 (2%) | > 10 (− 6%) |
| 8 | 5F-AMB | > 10 (14%) | > 10 (− 6%) | > 10 (1%) | > 10 (− 5%) |
| 9 | FUB-AMB | > 10 (4%) | > 10 (17%) | > 10 (− 2%) | > 10 (11%) |
| 10 | MA-CHMINACA | > 10 (2%) | > 10 (31%) | > 10 (19%) | > 10 (10%) |
| 11 | 5F-ADB | > 10 (0%) | > 10 (6%) | > 10 (10%) | > 10 (− 10%) |
| 12 | MDMB-FUBINACA | > 10 (− 4%) | > 10 (30%) | > 10 (18%) | > 10 (31%) |
| 13 | MDMB-CHMICA | > 10 (5%) | > 10 (38%) | > 10 (5%) | 14.1 ± 3.1a |
| 14 | MDMB-CHMINACA | > 10 (− 5%) | 10.3 ± 1.7 | > 10 (27%) | ≈ 10 (51%) |
| 15 | 5F-ABPICA | > 10 (10%) | > 10 (− 6%) | > 10 (23%) | > 10 (− 25%) |
| 16 | 5F-AB-PINACA | > 10 (15%) | > 10 (− 3%) | > 10 (12%) | > 10 (10%) |
| 17 | 5Cl-AB-PINACA | > 10 (17%) | > 10 (− 8%) | > 10 (4%) | > 10 (0%) |
| 18 | AB-FUBINACA (3F-benzyl-isomer) | > 10 (11%) | > 10 (− 7%) | > 10 (10%) | > 10 (− 11%) |
| 19 | AB-FUBINACA (2F-benzyl-isomer) | > 10 (15%) | > 10 (− 9%) | > 10 (11%) | > 10 (− 5%) |
| 20 | AB-CHMINACA | > 10 (8%) | > 10 (− 3%) | > 10 (13%) | > 10 (11%) |
| 21 | 5F-ADBICA | > 10 (8%) | > 10 (− 8%) | > 10 (27%) | > 10 (− 11%) |
| 22 | ADB-CHMICA | > 10 (17%) | > 10 (8%) | > 10 (8%) | > 10 (14%) |
| 23 | 5F-ADB-PINACA | > 10 (18%) | > 10 (− 2%) | > 10 (9%) | > 10 (21%) |
| 24 | ADB-FUBINACA | > 10 (7%) | > 10 (− 3%) | > 10 (7%) | > 10 (16%) |
| 25 | MAB-CHMINACA | > 10 (16%) | > 10 (− 7%) | > 10 (6%) | > 10 (10%) |
| 26 | 5F-ADB-PINACA-isomer 2 | > 10 (2%) | > 10 (− 6%) | > 10 (8%) | > 10 (− 11%) |
| 27 | PX-1 | > 10 (6%) | > 10 (1%) | > 10 (15%) | > 10 (− 16%) |
| 28 | PX-2 | > 10 (16%) | > 10 (− 10%) | > 10 (− 4%) | > 10 (15%) |
| 29 | APP-FUBINACA | > 10 (26%) | > 10 (− 9%) | > 10 (4%) | > 10 (21%) |
| 30 | APP-CHMINACA | > 10 (11%) | > 10 (9%) | > 10 (5%) | ≈ 10 (57%) |
| 31 | Cumyl-PICA | > 10 (11%) | > 10 (3%) | > 10 (19%) | > 10 (− 7%) |
| 32 | 5F-Cumyl-PICA | > 10 (14%) | > 10 (− 6%) | > 10 (16%) | > 10 (− 3%) |
| 33 | Cumyl-THPINACA | > 10 (11%) | > 10 (7%) | > 10 (11%) | > 10 (9%) |
| Ester-substituted indazoles (B) | |||||
| 34 | MO-CHMINACA | > 10 (1%) | 9.29 ± 1.7 | > 10 (0%) | 12.6 ± 3.5a |
| 3-Carbonyl-indoles (C) | |||||
| 35 | FUB-JWH-018 | > 10 (7%) | > 10 (30%) | > 10 (20%) | > 10 (30%) |
| 36 | F-2201 | > 10 (− 10%) | 22.1 ± 12.2a | > 10 (18%) | > 10 (14%) |
| 37 | Cl-2201 | > 10 (− 1%) | 7.12 ± 1.26 | > 10 (16%) | > 10 (4%) |
| 3-Carbonyl-carbazoles (E) | |||||
| 39 | EG-018 | > 10 (0%)b | > 10 (1%)b | > 10 (2%)b | > 10 (− 11%) |
| 40 | EG-2201 | > 10 (− 3%) | > 10 (3%) | > 10 (3%) | > 10 (7%) |
| 41 | MDMB-CHMCZCA | > 10 (− 8%) | > 10 (25%) | > 10 (− 35%) | 9.66 ± 1.20a |
| Carbonyl-benzimidazole (F) | |||||
| 42 | FUBIMINA | > 10 (16%) | > 10 (44%) | > 10 (42%)c | >10 (14%)b |
aExtrapolated values; full curve could not be determined due to limited solubility
bn = 2
cn = 1