Table 2.
Functional Selectivity for 5-HT2C-Selective Agonistsa
| Compd. | Gq calcium flux | β-arrestin-2 | ||||
|---|---|---|---|---|---|---|
| pEC50 ( EC50, nM) |
Emax (%) |
Log(Emax / EC50) | pEC50 ( EC50, nM) |
Emax (%) |
Log(Emax / EC50) | |
| 5-HT | 9.74 ± 0.02 (0.18) |
100 ± 0.9 | 9.85 | 7.82 ± 0.03 (15) |
100 ± 1.0 | 7.82 |
| Lorcaserin | 8.68 ± 0.04 (2.1) |
101 ± 1.4 | 8.68 | 7.40 ± 0.05 (40) |
97 ± 2.1 | 7.38 |
| (+)−15a | 7.64 ± 0.05 (23) |
71 ± 1.4 | 7.49 | NA | NA | - |
| (+)−19 | 7.62 ± 0.04 (24) |
92 ± 1.3 | 7.58 | 7.16 ± 0.04 (70) |
43 ± 0.9 | 6.79 |
| (−)−19 | 6.99 ± 0.05 (103) |
104 ± 2.1 | 7.00 | > 1,000 | ND | - |
| (+)−32 | 6.92 ± 0.06 (120) |
60 ± 0.7 | 6.70 | NA | NA | - |
| (+)−40 | 8.04 ± 0.04 (9.2) | 97 ± 1.3 | 8.02 | 7.64 ± 0.05 (22.7) |
56 ± 1.0 | 7.39 |
| (+)−41 | 8.62 ± 0.03 (2.4) |
93 ± 1.1 | 8.59 | 7.96 ± 0.05 (11) |
54 ± 1.0 | 7.69 |
a
Data were acquired with the human 5-HT2C-INI receptor isoform measuring Gq calcium flux (FLIPR) and β-arrestin-2 recruitment (Tango). Emax values are shown as the mean ± SEM (n = 3), and assays were conducted in parallel with the same drug dilutions. “NA” indicates no activity up to 10 μM. “ND” indicates not determined because of no saturable Emax.