Table 1.
Cannabinoid receptor binding and in vivo effects of 1-pentyl-3-phenylacetylindoles, unsubstituted and with methyl and methoxy substituents at various positions on the phenyl ring.
| Compound | * R | * R′ | Affinities (nM)a | In Vivo ED50s (μmol/kg)** | Avg. Potency | |||
|---|---|---|---|---|---|---|---|---|
| CB1 | CB2 | SA | %MPE | RT | ||||
| Δ9-THC | ----- | ----- | 41b (2) | 36c (10) | 0.9 d | 2.6 d | 2.6 d | 2.0 |
| JWH-018 | Naphthoyl | H | 9d (5) | 3 (3) | 0.3d | ~ 0.09d | 1.8d | 0.7 |
| JWH-167 | Phenyl | H | 90 (17) | 159 (14) | 1.6 (0.9–2.6) | 1.3 (0.7–2.3) | 13 (7–23) | 5.3 |
| JWH-205 | Phenyl | CH3 | 134 (23) | 180 (9) | 19 (9–34) | 13 (9–19) | 13 (9–16) | 15 |
| JWH-251 | 2-Methylphenyl | H | 29 (3) | 146 (36) | 0.9 (0.6–1.6) | 0.9 (0.6–1.3) | 6 (3–9) | 2.6 |
| JWH-252 | 2-Methylphenyl | CH3 | 23 (3) | 19 (0.6) | NT | NT | NT | --- |
| JWH-208 | 4-Methylphenyl | H | 179 (10) | 570 (127) | 2.8 (0.9–9) | 16 (9–25) | 38 (22–63) | 18.9 |
| JWH-209 | 4-Methylphenyl | CH3 | 746 (49) | 1353 (270) | 39 (21–75) | 57 (33–99) | 81 (42–153) | 59 |
| JWH-250 | 2-Methoxyphenyl | H | 11 (2) | 33 (3) | NT | NT | NT | --- |
| JWH-306 | 2-Methoxyphenyl | CH3 | 25 (1) | 82 (11) | 87% (2.9 μg/kg) | 1.1 (0.9–1.4) | 1.1 (0.9–1.7) | 1.1 |
| JWH-302 | 3-Methoxyphenyl | H | 17 (2) | 89 (15) | 0.6 (0.3–1.2) | 0.9 (0.6–1.2) | 3 (2.1–4.2) | 1.5 |
| JWH-253 | 3-Methoxyphenyl | CH3 | 62 (10) | 33 (3) | NT | NT | NT | --- |
| JWH-201 | 4-Methoxyphenyl | H | 1064 (21) | 444 (14) | 84% (90 μg/kg) | 35% (90 μg/kg) | −2.3 (90 μg/kg) | --- |
| JWH-202 | 4-Methoxyphenyl | CH3 | 1678 (62) | 645 (6) | 26 (11–51) | 51 (29–97) | −2.5 (86 μg/kg) | 38.5 |
*
See Figure 1.
**
SA = spontaneous activity, %MPE = % maximum possible antinociceptive effect, RT = rectal temperature, NT = not tested. Values shown are ED50s (95% confidence intervals). Single dose tests are indicated by magnitude of effect and dose (in parentheses). Average potency was calculated as the average of all ED50 values for the compound.
a
(Huffman et al., 2005a) CB1 and CB2 affinities of all 1-pentyl-3-phenylacetylindoles presented first in this publication. Values shown are Ki (± SEM).