Affinities for cariprazine and aripiprazole at various receptors, channels, transporters, and enzymes
Cariprazine and aripiprazole demonstrated negligible (percentage displacement less than 20% at 1 μM test concentration) affinities for adenosine A1, A2A, and A3; adrenergic α2B, α2C; cannabinoid CB1 and CB2; cholecystokinin CCK1 and CCK2; corticotropin (CRF1); dopamine D1, D4.2, D5; estrogen ERα and ERβ; GABA (A and B), galanin (GAL1 and GAL2) glucocorticoid; glutamate (α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, N-methyl-d-aspartate); 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, 5-HT5A, 5-HT6; sigma σ2 receptors; Ca2+ L-type (benzothiazepine and phenylalkylamine); Ca2+ N-type, sodium (site 1 and site-2) channels; norepinephrine, adenosine, choline transporters. Cariprazine did not inhibit (inhibition <10% at 10 μM test concentration) Ca2+-ATPase; Na+/K+-ATPase; acetylcholinesterase; HMG-CoA reductase; acyl-CoA-cholesterol acyltransferase.
| Receptor | Species | Source | Radioliganda | pKi | |
|---|---|---|---|---|---|
| Cariprazine | Aripiprazole | ||||
| D3 | Human | CHO cells | [3H]Spiperone (0.7) | 10.07 | 9.03 |
| Rat | Sf9 | [3H]Spiperone (0.85) | 9.15 | 8.47 | |
| D2S | Human | CHO cells | [3H]Spiperone (0.16) | 9.16 | 9.72 |
| D2L | Human | CHO cells | [3H]Spiperone (0.16) | 9.31 | 9.68 |
| D2 | Rat | Striatum | [3H]Spiperone (0.7) | 8.03 | 8.20 |
| 5-HT1A | Human | CHO cells | [3H]8-OH-DPAT (1.5) | 8.59 | 8.97 |
| 5-HT1A | Rat | Hippocampus | [3H]8-OH-DPAT (2.0) | 8.34 | 8.20 |
| 5-HT2A | Human | CHO-K1 cells | [3H]Ketanserine (0.5) | 7.73 | 8.75 |
| 5-HT2A | Rat | Frontal cortex | [3H]Ketanserine (1.1) | 7.26 | 7.64 |
| 5-HT2B | Human | CHO-K1 cells | [3H]LSD (1.2) | 9.24 | 9.60 |
| 5-HT2C | Human | CHO-K1 cells | [3H]Mesulergine (1.0) | 6.87 | 7.81 |
| 5-HT6 | Human | HeLa cells | [3H]LSD (1.5) | <6.0 | 7.23 |
| 5-HT7 | Human | CHO cells | [3H]LSD (1.5) | 6.95 | n.d. |
| H1 | Human | CHO-1 cells | [3H]Pyrilamine (1.2) | 7.63 | 9.07 |
| α1A-AR | Rat | Submax. gland | [3H]Prazosin (0.25) | 6.88 | 7.31 |
| α1B-AR | Rat | Liver | [3H]Prazosin (0.25) | <6.0b | n.d. |
| α1D-AR | Human | HEK-293 | [3H]Prazosin (0.6) | 6.68 | n.d. |
| α2A-AR | Human | Sf9 | [3H]MK-912 (1.0) | <6.0b | 7.55 |
| β -AR | Human | Brain | [3H]DHA (0.25) | <6.0b | 7.44 |
| σ1 | Human | Jurkat cells | [3H]Haloperidol (8.0) | 7.74 | 7.07 |
| DAT | Human | CHO cells | [125I]RTI-55 (0.15) | <6.0 | 6.75 |
| SERT | Human | HEK-293 cells | [125I]RTI-55 (0.15) | <6.0 | 7.38 |
DHA, dihydroalprenolol; LSD, lysergic acid diethylamide; DAT, dopamine transporter; SERT, serotonin transporter; n.d., not determined.
↵a Numbers in parentheses are in nM.
↵b Cariprazine resulted in 65, 50, and 64% displacement at α1B-AR a2A-AR and β -AR receptors, respectively, in concentration of 1 μM.