TABLE 2

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.

ReceptorSpeciesSourceRadioligandapKi
CariprazineAripiprazole
D3HumanCHO cells[3H]Spiperone (0.7)10.079.03
RatSf9[3H]Spiperone (0.85)9.158.47
D2SHumanCHO cells[3H]Spiperone (0.16)9.169.72
D2LHumanCHO cells[3H]Spiperone (0.16)9.319.68
D2RatStriatum[3H]Spiperone (0.7)8.038.20
5-HT1AHumanCHO cells[3H]8-OH-DPAT (1.5)8.598.97
5-HT1ARatHippocampus[3H]8-OH-DPAT (2.0)8.348.20
5-HT2AHumanCHO-K1 cells[3H]Ketanserine (0.5)7.738.75
5-HT2ARatFrontal cortex[3H]Ketanserine (1.1)7.267.64
5-HT2BHumanCHO-K1 cells[3H]LSD (1.2)9.249.60
5-HT2CHumanCHO-K1 cells[3H]Mesulergine (1.0)6.877.81
5-HT6HumanHeLa cells[3H]LSD (1.5)<6.07.23
5-HT7HumanCHO cells[3H]LSD (1.5)6.95n.d.
H1HumanCHO-1 cells[3H]Pyrilamine (1.2)7.639.07
α1A-ARRatSubmax. gland[3H]Prazosin (0.25)6.887.31
α1B-ARRatLiver[3H]Prazosin (0.25)<6.0bn.d.
α1D-ARHumanHEK-293[3H]Prazosin (0.6)6.68n.d.
α2A-ARHumanSf9[3H]MK-912 (1.0)<6.0b7.55
β -ARHumanBrain[3H]DHA (0.25)<6.0b7.44
σ1HumanJurkat cells[3H]Haloperidol (8.0)7.747.07
DATHumanCHO cells[125I]RTI-55 (0.15)<6.06.75
SERTHumanHEK-293 cells[125I]RTI-55 (0.15)<6.07.38
  • 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.