Table 1.
Comparison of CB2R affinity (Ki), potency for AC-Inhibition (IC50) and Fractional Receptor Occupancy (FRO) for 50% AC-Inhibition for JWH-018, JWH-073 and metabolites
| Drug | CB2R Affinity (Ki, nM) |
Potency for AC-Inhibition (IC50, nM) |
FRO for 50% AC-Inhibition (%)a |
|
|---|---|---|---|---|
| CP-55,940 | 0.4 ± 0.2 (3) | 3.3 ± 1.4 (5) | 81.7 ± 6.7 (5) | |
| Δ9-THC | 14.8 ± 1.5 (3) | 57.9 ± 19.8 (5) | 71.7 ± 7.8 (5) | |
| JWH-018 | 5.6 ± 2.4 (3) | 3.6 ± 2.2 (6) | 19.0 ± 5.3 (5) | |
| M1 | 20.9 ± 5.1 (4) | N.D. | N.D. | |
| M2 | 115.1 ± 23.4 (3) | N.D. | N.D. | |
| M3 | 69.3 ± 3.2 (3) | N.D. | N.D. | |
| M5 | 47.4 ± 10.1 (3) | 17.7 ± 5.5 (4) | 25.5 ± 7.2 (4) | |
| M6 | >10,000 (3) | N.D. | N.D. | |
| M7 | 83.7 ± 10.6 (3) | N.D. | N.D. | |
| JWH-073 | 9.8 ± 0.9 (4) | 16.9 ± 1.9 (5) | 62.5 ± 3.0 (5) | |
| M1 | 73.4 ± 6.7 (3) | N.D. | N.D. | |
| M2 | 184.7 ± 51.8 (8) | N.D. | N.D. | |
| M3 | 291.3 ± 96.9 (3) | N.D. | N.D. | |
| M5 | 96.0 ± 7.1 (3) | 13.3 ± 2.0 (3) | 12.1 ± 1.6 (3) | |
| M6 | >10,000 (3) | N.D. | N.D. | |
| M7 | 31.4 ± 6.7 (3) | N.D. | N.D. | |
The data are presented as the mean ± SEM (number of replications)
a
The formula employed to calculate FRO = [DRUG] / (Ki + [DRUG]) (Tallarida, 1990)
N.D. = Not determined