Table 2.
Summary of functional activity data for cariprazine (CAR), desmethyl-cariprazine (DCAR), and didesmethyl-cariprazine (DDCAR)
| Assay | CAR | DCAR | DDCAR | |||
|---|---|---|---|---|---|---|
| Emax (%) | pEC50/pKB | Emax (%) | pEC50/pKB | Emax (%) | pEC50/pKB | |
| In vitro [35S]GTPγS binding | ||||||
| Human membranes | ||||||
| hD2 agonism | No stimulation | n.t. | No stimulation | |||
| hD3 agonism | No stimulation | n.t. | No stimulation | |||
| hD2 antagonisma | 9.12±0.15 | n.t. | 9.02±0.04 | |||
| hD3 antagonisma | 9.50±0.07 | n.t. | 10.04±0.17 | |||
| h5-HT1A agonism | 34±3 | 8.64±0.16 | n.t. | 65±13 | 7.51±0.18 | |
| Rat membranes | ||||||
| Striatum (D2) | ||||||
| Agonism | No stimulation | n.t. | No stimulation | |||
| Antagonisma | 8.90±0.10 | n.t. | 9.27±0.11 | |||
| Hippocampus (5-HT1A) | ||||||
| Agonism | 44±4 | 7.05±0.08 | n.t. | 94±4 | 7.08±0.15 | |
| cAMP signaling | ||||||
| hD2 agonism | 78±3 | 9.00±0.10 | 71±1 | 8.90±0.10 | 71±4 | 8.70±0.10 |
| hD3 agonism | 71±4 | 8.57±0.30 | 74±2 | 8.09±0.03 | 82±4 | 8.17±0.18 |
| h5-HT1A agonism | 95±11 | 6.80±0.07 | 70±10 | 6.28±0.13 | 99±13 | 7.32±0.07 |
| Ca2+ release | ||||||
| h5-HT2B agonism | No stimulation | No stimulation | No stimulation | |||
| h5-HT2B antagonismb | 8.50±0.19 | 8.36±0.19 | 8.67±0.09 | |||
Notes: Data are the mean±standard error of the mean from three to six independent experiments in duplicate or triplicate. aFor antagonist action, pKB values are given. bpIC50 values.
Abbreviations: Emax (%), percent maximal stimulation relative to 10 μM dopamine or 1 μM serotonin; n.t., not tested; pEC50, negative logarithm of concentration of a drug that gives half-maximal response.