Table 2.
Pharmacology of 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2 and DOC at 5-HT1A, 5-HT2A and 5-HT2C receptors: Effects on binding and function.
| 5-HT1A | 5-HT2A | 5-HT2C | |||||
|---|---|---|---|---|---|---|---|
| Drug | [3H]8-OH-DPAT binding Ki (nM) ± sem | Function [35S]GTPγS Binding EC50 (nM) EC50 (nM) ± sem % maximal effecta | [125I]DOI binding Ki (nM) ± sem | Function [3H]AA release EC50 (nM) ± sem % maximal effecta | Function IP-1 formation EC50 (nM) ± sem % maximal effecta | [125I]DOI binding Ki (nM) ± sem | Function IP-formation EC50 (nM) ± sem % maximal effecta |
| 2C-C | 740 ± 170 | >10 μM* | 5.47 ± 0.68 | 13.9 ± 6.1 | 40.1 ± 4.7 | 5.4 ± 1.2 | 24.2 ± 5.6 |
| <25% | 64.2 ± 2.2% | 102.1 ± 5.5% | 93.5 ± 6.5% | ||||
| 2C-D | 1630 ± 150 | >10 μM* | 23.9 ± 3.9 | 153 ± 28 | 145 ± 39 | 12.7 ± 1.3 | 71.1 ± 8.0 |
| <25% | 81.1 ± 9.7% | 93.0 ± 6.7% | 100 ± 14% | ||||
| 2C-E | 1190 ± 250 | >10 μM* | 4.50 ± 0.71 | 7.1 ± 3.3 | 84 ± 16 | 5.4 ± 1.1 | 18.0 ± 5.9 |
| <20% | 65 ± 11% | 125 ± 13% | 98 ± 16% | ||||
| 2C-I | 970 ± 430 | 4900 ± 2000 | 9.3 ± 3.2 | ND | 7.9 ± 2.2 | 10.2 ± 1.7 | 2.8 ± 1.0 |
| 102.1 ± 4.7% | 32.5 ± 1.5% | 82.4 ± 6.4% | 79 ± 16 | ||||
| 2C-T-2 | 1740 ± 660 | 3000 ± 1300 | 12.5 ± 4.4 | 2.30 ± 0.69 | 7.9 ± 2.0 | 14.2 ± 3.6 | 3.8 ± 1.1 |
| 76 ± 10% | 106.6 ± 6.3% | 87.4 ± 6.5% | 93.0 ± 1.8% | ||||
| DOC | >9200 | >10 μM* | 4.00 ± 0.45 | 2.91 ± 0.66 | 10.5 ± 2.6 | 3.57 ± 0.56 | 14.6 ± 3.0 |
| <10% | 81 ± 16% | 102.4 ± 4.2% | 97 ± 19% | ||||
| Serotonin | 4.3 ± 1.0 | 15.7 ± 5.4 | 25.8 ± 4.6 | 7.8 ± 2.0 | 43 ± 10 | 3.74 ± 0.71 | 1.94 ± 0.49 |
| 105.3 ± 2.2% | 100% | 99.7 ± 0.9% | 93.9 ± 2.0% | ||||
| LSD | 2.50 ± 0.95 | 6.4 ± 1.8 | 0.47 ± 0.12 | 1.01 ± 0.31 | 0.264 ± 0.052 | 3.22 ± 0.57 | 1.14 ± 0.36 |
| 109.6 ± 4.5% | 87.8 ± 3.4% | 80.3 ± 4.9% | 74.6 ± 9.1% | ||||
| DOM | 11900 ± 5600 | 13900 ± 1500 | 8.1 ± 2.2 | 31.2 ± 9.6 | 25.9 ± 4.2 | 8.4 ± 3.0 | |
| 53.8 ± 9.7% | 106 ± 11% | 94 ± 14% | |||||
| DMT | 400 ± 190 | 1490 ± 570 | 201 ± 48 | 260 ± 120 | 269 ± 61 | 111 ± 34 | 114 ± 35 |
| 100.4 ± 5.2% | 105.1 ± 3.0% | 39.0 ± 4.6% | 99 ± 11% | ||||
| MDMA | 11900 ± 1200 | 36000 ± 16000 | 20900 ± 4600 | 5.5 ± 2.3 mM | 9600 ± 2400 | 9100 ± 1500 | |
| 64.3 ± 9.4% | 40.2 ± 7.1% | 92.2 ± 8.0% | |||||
| METH | 9700 ± 1800 | 23600 ± 8100 | 41900 ± 9600 | >1 mMa | 10100 ± 3200 | 74000 ± 16000 | |
| 68 ± 11% | <3% | 52 ± 10% | |||||
For test compounds, n=3–11 for each assay. Data are expressed as mean ± S.E.M. Hill slopes for 5-HT1A [3H]8-OH-DPAT binding ranged from −0.73 to −1.04, for 5-HT2A [125I]DOI binding ranged from −0.53 to −1.10 and for 5-HT2C [125I]DOI binding ranged from −0.65 to −1.32.
ND- the EC50 value was not determined. 2C-I was an antagonist at the 5-HT2A [3H]AA release functional assay, with an IC50 of 2060 ± 860 nM and 84 ± 11% inhibition, compared to the maximal inhibition by ketanserin, of 100 nM serotonin stimulation.
These compounds also had minimal effect as antagonists at the 5-HT1A receptor, with maximal inhibition <30% of the maximal inhibition by WAY 100,635.
Maximal effect of each drug was normalized to the maximal effect of serotonin.