Table 3.
Pharmacology of 2C-C, 2C-D, 2C-E, 2C-I, 2C-T-2 and DOC at DAT, SERT and NET: Effects on binding and function.
| HEK-hDAT cells | HEK-hSERT cells | HEK-hNET cells | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Drug | [125I]RTI-55 binding Ki, nM | [3H]Dopamine uptake IC50, nM | [3H]Dopamine release EC50, nM % METH maximal effect | [125I]RTI-55 binding Ki, nM | [3H]Serotonin uptake IC50, nM | [3H]Serotonin release EC50, nM % PCA maximal effect | [125I]RTI-55 binding Ki, nM | [3H]NE uptake IC50, nM | [3H]NE release EC50, nM % METH maximal effect |
| 2C-C | >10 μM | >10 μM | ND Minimal |
>10 μM | >9600# | ND Minimal |
>7600# | >9500 | ND Minimal |
| 2C-D | >10 μM | >10 μM | ND Minimal |
>10 μM | >8400# | ND Minimal |
>8500# | >9200 | ND Minimal |
| 2C-E | >10 μM | >10 μM | ND Minimal |
>10 μM | >7500# | ND Minimal |
>7600# | >9800 | ND Minimal |
| 2C-I | >10 μM | >9600# | ND Minimal |
950 ± 440 | 5600 ± 2100 | ND Minimal |
>10 μM | >8200# | ND Minimal |
| 2C-T-2 | >10 μM | >10 μM | ND Minimal |
>9400# | >8600# | ND Minimal |
>10 μM | >7200# | ND Minimal |
| DOC | >10 μM | >10 μM | ND Minimal |
>10 μM | >8600# | ND Minimal |
>7700# | >8400# | ND Minimal |
| Cocaine | 462 ± 97 | 374 ± 36 | ND Minimal |
321 ± 26 | 383 ± 49 | ND Minimal |
1280 ± 150 | 332 ± 29 | ND Minimal |
| METH | 4750 ± 530 | 56 ± 15 | 970 ± 250a 100% |
188000 ± 14000 | 4100 ± 1300 | 27800 ± 7700a | 1480 ± 130 | 23.0 ± 5.5 | 67 ± 18 a 100% |
| LSD | >10 μM | >10 μM | >10 μM | >10 μM | 5600 ± 260 | >10 μM | |||
Abbreviations: NE, norepinephrine, PCA. p–chloroamphetamine. Hill slopes for [125I]RTI-55 binding ranged from −0.97 to −1.05 for hDAT, −0.70 to −1.15 for hSERT and −0.99 to −2.13 for hNET.
For test compounds, n=2 (when >10 μM) to 7. Data are expressed as mean ± S.E.M. The standard compounds were, for purposes of comparison, cocaine for the binding and uptake assays, methamphetamine for [3H]dopamine and [3H]norepinephrine release and PCA for [3H]serotonin release. The EC50 value for PCA for stimulating [3H]serotonin release was 1350 ± 420 nM.
If some experiments yielded IC50 or Ki values less than 10 μM and other experiments yielded IC50 or Ki values greater than 10 μM, the latter experiments were assigned a value of 10 μM and averages calculated (n≥3). The actual value is greater than that average and no standard error is reported.
ND- The EC50 value could not be determined.
Values from Gatch et al., 2011.