Table 1.
Functional profiling of numerous 5-HT2CR agonists and respective profiles at the 5-HT2AR and 5-HT2BR to show subtype selectivity among 5-HT2Rs.
| Compound | 5-HT2CR | 5-HT2AR | 5-HT2BR | Refs. | |||||
|---|---|---|---|---|---|---|---|---|---|
| EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | 2A/2C ratio | 2B/2C ratio | ||
| 5-HT (1) | 3.48 | 100 | 14.04 | 100 | 20 ± 2.8 | 100 | 4.03 | 5.75 | [95] |
| RO 60–0175 (2) | 52 ± 3 | 88 ± 20 | 400 ± 20 | 91 ± 5 | 2.4 ± 1 | 130 ± 30 | 7.69 | 0.05 | [96] |
| YM-348 (3) | 1.0 ± 0.2 | 76 ± 1 | 93 ± 10 | 97 ± 2 | 3.2 ± 3 | 110 ± 10 | 93.0 | 3.2 | [97] |
| d-fenfluramine (4) | 300 ± 29 | 90 ± 9 | 720 ± 77 | 80 ± 4 | 23 ± 4 | 100 ± 10 | 2.4 | 0.08 | [98] |
| 5 | 4.2 | 87 | 374 | 56 | NE | NE | 89.0 | - | [99] |
| 6 | 8.7 | 97 ± 1 | 491 | 21 ± 0 | 1745 | 35 ± 7 | 57.1 | 200.6 | [100] |
| 7 | 7.65 | 71 | 6.57 | 79 | 7.05 | 54 | 0.86 | 0.92 | [101] |
| 8 | 7.63 | 92 | NE | NE | 6.86 | 63 | - | 0.90 | [63] |
| mCPP (9) | 120 ± 10 | 63 ± 3 | 150 ± 20 | 18 ± 2 | 93 ± 50 | 21 ± 9 | 1.25 | 0.78 | [97] |
| CP-809101 (10) | 0.11 | 93 | 153 | 67 | 65.3 | 57 | 1391 | 593.6 | [102] |
| 11 | 1.1 ± 0.4 | 90 | 127 ± 82 | 100 | 94 ± 68 | 50 | 115.5 | 85.5 | [103] |
| 12 | 3.3 ± 1.8 | 90 | 128 ± 44 | 100 | 414 ± 468 | 130 | 38.8 | 125.5 | [103] |
| 13 | 36 | 100 | 707 | 100 | >10000 | - | 19.6 | >277.8 | [104] |
| lorcaserin (14) | 9 ± 0.5 | 100 | 168 ± 11 | 75 | 943 ± 90 | 100 | 18.7 | 104.8 | [51] |
| vabicaserin (15) | 8 | 100 | 1650 | -a | >10,000 | 80 | 206.3 | 0.19 | [105] |
| WAY-163909 (16) | 8 ± 3 | 90 ± 6 | NE | NE | 185 ± 105 | 40 ± 3 | - | 23.1 | [63] |
| PF-04781340 (17) | 9 | 99 | - | - | 1484 | 69 | - | 164 | [106] |
| PF-4522654 (18) | 16 | 58 | NE | NE | >10000 | <10 | - | >625 | [107] |
| 19 | 95 | 76 | 2634 | 21 | 503 | 31 | 27.7 | 5.3 | [108] |
| 20 | 5 ± 3 | - | 635 ± 862 | - | 48 ± 41 | - | 127 | 9.6 | [109] |
a
Functional output indicated antagonist activity; Values with error represent the mean ± SD; For 5-HT2AR and 5-HT2BR, large reported errors indicate inconsistent results from compounds showing no effect and intermittent positive effects; No effect (NE); Not applicable or not tested (−).