Affinities of S33005 as compared with reference antidepressant agents at monoamine transporters and at monoaminergic receptors known to modulate cerebral monoaminergic transmission
| Species | Radioligand (nM) | Tissue | S33005 | Venlafaxine | Clomipramine | Citalopram | Reboxetine | |
|---|---|---|---|---|---|---|---|---|
| SERT | Rat | [3H]Paroxetine (2) | Frontal cortex | 8.71 ± 0.06 | 7.61 ± 0.06 | 8.92 ± 0.23 | 8.82 ± 0.03 | 6.79 ± 0.19 |
| (1.9) | (24.5) | (1.2) | (1.5) | (162) | ||||
| SERT | Human | [3H]Paroxetine (2) | HEK293 cell line | 8.67 ± 0.18 | 7.12 ± 0.05 | 9.86 ± 0.11 | 8.33 ± 0.25 | 6.97 ± 0.22 |
| (2.1) | (75.9) | (0.14) | (4.7) | (107) | ||||
| NET | Rat | [3H]Nisoxetine (2) | Frontal cortex | 6.75 ± 0.11 | 6.00 ± 0.09 | 7.57 ± 0.09 | 5.42 ± 0.05 | 8.28 ± 0.18 |
| (178) | (1000) | (26.9) | (3800) | (5.2) | ||||
| NET | Human | [3H]Nisoxetine (2) | MDCK cell line | 5.82 ± 0.09 | 5.20 ± 0.10 | 7.27 ± 0.08 | <5 | 7.80 ± 0.04 |
| (1510) | (6310) | (53.7) | (15.8) | |||||
| DAT | Rat | [3H]GR12935 (2) | Striatum | <5 | <5 | 5.91 ± 0.31 | <5 | <5 |
| (1230) | ||||||||
| DAT | Human | [3H]GR12935 (2) | CHO cell line | <5 | <5 | 5.52 ± 0.02 | <5 | <5 |
| (3020) | ||||||||
| 5-HT1A | Human | [3H]8-OH-DPAT (0.4) | CHO cell line | <5 | <5 | <5 | <5 | <5 |
| 5-HT1B | Human | [3H]GR125,743 (1.0) | CHO cell line | <5 | <5 | <5 | <5 | <5 |
| 5-HT1D | Human | [3H]GR125,743 (1.0) | CHO cell line | <5 | <5 | <5 | <5 | <5 |
| 5-HT2A | Human | [3H]Ketanserin (0.5) | CHO cell line | <5 | <5 | 7.45 ± 0.10 | <5 | <5 |
| (35.5) | ||||||||
| 5-HT2C | Human | [3H]Mesulergine (1.0) | CHO cell line | <5 | <5 | 7.19 ± 0.11 | 6.21 ± 0.12 | 6.34 ± 0.07 |
| (64.6) | (617) | (457) | ||||||
| 5-HT3 | Mouse | [3H]BRL43694 (1.0) | NE-15 cell line | <5 | <5 | 6.07 ± 0.17 | <5 | <5 |
| (85.1) | ||||||||
| α1-AR | Rat | [3H]Prazosin (0.2) | Frontal cortex | <5 | <5 | 7.81 ± 0.18 | <5 | <5 |
| (15.5) | ||||||||
| hα1A-AR | Human | [3H]Prazosin (0.1) | CHO cell line | <5 | <5 | 8.49 ± 0.10 | <5 | <5 |
| (3.2) | ||||||||
| α2-AR | Rat | [3H]RX821,002 (0.40) | Cortex | <5 | <5 | <5 | <5 | <5 |
| α2A-AR | Human | [3H]RX821,002 (0.4) | CHO cell line | <5 | <5 | 6.28 ± 0.281-a | <5 | <5 |
| (525) | ||||||||
| D2 | Human | [3H]Spiperone (0.1) | CHO cell line | <5 | <5 | 7.11 ± 0.091-a | <5 | <5 |
| (77.6) | ||||||||
| D3 | Human | [3H]Spiperone (0.3) | CHO cell line | <5 | <5 | 7.30 ± 0.091-a | <5 | <5 |
| (50.1) |
MDCK, Madin-Darby canine kidney cells.
Data are presented as mean ± S.E.M. pKi of 3 to 4, or
↵1-a means ± range of two independent determinations, each performed in triplicate. In addition, equivalent Ki values are indicated in parentheses: a pKi of <5 corresponds to a Ki of >10,000 nM.