Table 1.
In vitro receptor binding affinities of cariprazine (CAR), desmethyl-cariprazine (DCAR), and didesmethyl-cariprazine (DDCAR)
| Receptor | Cell or tissue source | Binding affinity, pKi | ||
|---|---|---|---|---|
| CARa | DCAR | DDCAR | ||
| Humanb | ||||
| Dopamine D3 | CHO cells | 10.07 | 10.42 | 10.25 |
| Dopamine D2L | CHO cells | 9.31 | 9.09 | 8.85 |
| Serotonin 5-HT2B | CHO-K1 cells | 9.24 | 9.33 | 9.28 |
| Dopamine D2S | CHO cells | 9.16 | 8.88 | 8.58 |
| Serotonin 5-HT1A | CHO cells | 8.59 | 8.53 | 8.77 |
| σ1 | Jurkat cells | 7.74 | 8.02 | 8.02 |
| Serotonin 5-HT2A | CHO K1 cells | 7.73 | 7.93 | 7.94 |
| Histamine H1 | CHO cells | 7.63 | 7.74 | 7.63 |
| Serotonin 5-HT7 | CHO cells | 6.95 | n.t. | n.t. |
| Serotonin 5-HT2C | CHO cells | 6.87 | 7.13 | 7.07 |
| Serotonin 5-HT6 | HeLa cells | 40% | 7.02 | 6.93 |
| Ratc | ||||
| Dopamine D3 | Sf9 | 9.15 | 9.66 | 9.80 |
| Serotonin 5-HT1A | Hippocampus | 8.34 | 8.00 | 8.31 |
| Dopamine D2 | Striatum | 8.03 | 8.11 | 7.89 |
| Serotonin 5-HT2A | Frontal cortex | 7.26 | 7.50 | 7.37 |
| σ2 | Brain | 17%d | 28%d | 6.73 |
| Serotonin 5-HT2C | Ch. plexus | 6.76 | 6.97 | 7.04 |
| α1-AR | Cortex | 6.81 | 6.77 | 6.72 |
| α1A-AR | Submax. gland | 6.88 | 7.01 | 6.83 |
Notes: CAR, DCAR, and DDCAR produced 40–63% displacement at 1 μM test concentration for human α2A adrenergic, human dopamine D1, and rat β-adrenergic receptors. CAR, DCAR, and DDCAR demonstrated negligible affinities (percent displacement <20% at 1 µM test concentration) for adenosine A1, A2A, and A3; adrenergic α2B and α2C; cannabinoid CB1 and CB2; cholecystokinin CCK1 and CCK2; corticotropin (CRF1); dopamine D4.2 and D5; estrogen ERα and ERß; GABA (A and B), galanin (GAL1 and GAL2); glucocorticoid; glutamate (AMPA, kainate, NMDA); histamine (H2, H3 and H4); muscarinic (M1, M2, M3, M4, and M5); nicotinic; orphanin ORL1; opiate δ, κ, and μ; potassium channel HERG; progesterone; serotonin 5-HT3, 5-HT4, and 5-HT5A; Ca2+-L-type (benzothiazepine and phenylalkylamine); Ca2+-N-type, sodium (site 1 and site 2) channels; and norepinephrine, adenosine, and choline transporters. CAR, DCAR, and DDCAR did not inhibit (inhibition<10% at 10 µM test concentration) Ca2+-ATPase, Na+/K+-ATPase, acetylcholinesterase, HMG-CoA reductase, and acyl-CoA-cholesterol acyltransferase. aCAR values are republished with permission from Kiss B, Horváth A, Némethy Z, et al.Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010;333(1):328–340.12 bPerformed at MDS Pharma Services. cPerformed at Gedeon Richter Plc. dPercent displacement at 1 μM test concentration.
Abbreviations: ch. plexus, choroid plexus; CHO, Chinese hamster ovary; submax, submaxilliary.