Identification
NameCariprazine
Accession NumberDB06016
TypeSmall Molecule
GroupsApproved
Description

Cariprazine is an antipsychotic drug developed by Gedeon Richter and marketed by Actavis under the trade name Vraylar. Cariprazine acts as a D2 and D3 receptor partial agonist, with high selectivity towards the D3 receptor. This mechanism is relatively unique, since many other antipsychotics are D2 and 5-HT2A agonists. Cariprazine was approved by the FDA in September 2015 and is indicated in the treatment of schizophrenia and bipolar disorder. Action on the dopaminergic systems makes it also potentially useful as an add-on therapy in major depressive disorder.

Structure
Thumb
Synonyms
trans-N-{4-[2-[4-(2,3-dichlorophenyl)piperazine-1-yl]ethyl]cyclohexyl}-N’,N’-dimethylurea hydrochloride
External IDs MP-214 / RGH-188
Product Ingredients
IngredientUNIICASInChI KeyDetails
Cariprazine hydrochlorideKQD7C255YG 1083076-69-0GPPJWWMREQHLQT-BHQIMSFRSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VraylarCapsule, gelatin coated1.5 mg/1OralAllergan2015-09-17Not applicableUs
VraylarCapsule, gelatin coated6 mg/1OralAllergan2015-09-17Not applicableUs
VraylarCapsule, gelatin coated3 mg/1OralAllergan2015-09-17Not applicableUs
VraylarKitOralAllergan2015-09-17Not applicableUs
VraylarCapsule, gelatin coated4.5 mg/1OralAllergan2015-09-17Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIF6RJL8B278
CAS number839712-12-8
WeightAverage: 427.41
Monoisotopic: 426.1953171
Chemical FormulaC21H32Cl2N4O
InChI KeyKPWSJANDNDDRMB-QAQDUYKDSA-N
InChI
InChI=1S/C21H32Cl2N4O/c1-25(2)21(28)24-17-8-6-16(7-9-17)10-11-26-12-14-27(15-13-26)19-5-3-4-18(22)20(19)23/h3-5,16-17H,6-15H2,1-2H3,(H,24,28)/t16-,17-
IUPAC Name
3,3-dimethyl-1-[(1r,4r)-4-{2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl}cyclohexyl]urea
SMILES
CN(C)C(=O)N[[email protected]]1CC[[email protected]](CCN2CCN(CC2)C2=C(Cl)C(Cl)=CC=C2)CC1
Pharmacology
Indication

Cariprazine is an atypical antipsychotic indicated for the treatment of schizophrenia and for the acute treatment of manic or mixed episodes associated with bipolar I disorder.

Structured Indications
Pharmacodynamics

Cariprazine acts as a partial agonist at the dopamine D3 and D2 receptors with high binding affinity. Cariprazine acts as an antagonist at 5-HT2B and 5-HT2A receptors with high and moderate binding affinity as well as it binds to the histamine H1 receptors. Cariprazine shows lower binding affinity to the serotonin 5­ HT2C and α1A- adrenergic receptors and has no appreciable affinity for cholinergic muscarinic receptors.

Mechanism of action

The mechanism of action of cariprazine in schizophrenia and bipolar I disorder is unknown. However, the efficacy of cariprazine could be mediated through a combination of partial agonist activity at central dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Cariprazine forms two major metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), that have in vitro receptor binding profiles similar to the parent drug.

TargetKindPharmacological actionActionsOrganismUniProt ID
D(3) dopamine receptorProteinyes
agonist
partial agonist
HumanP35462 details
D(2) dopamine receptorProteinyes
agonist
partial agonist
HumanP14416 details
5-hydroxytryptamine receptor 1AProteinyes
agonist
partial agonist
HumanP08908 details
5-hydroxytryptamine receptor 2BProteinyes
antagonist
HumanP41595 details
5-hydroxytryptamine receptor 2AProteinyes
antagonist
HumanP28223 details
Histamine H1 receptorProteinyes
antagonist
HumanP35367 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding

Cariprazine and its metabolites are highly protein bound (91-97%).

Metabolism

Cariprazine is extensively metabolized by hydroxylation and demethylation. It is primarily metabolized by CYP3A4, and CYP2D6 to a lesser extent to active metabolites desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). DCAR is then further metabolized to DDCAR by CYP3A4 and CYP2D6, and DDCAR is then metabolized by CYP3A4 to a hydroxylated metabolite. Both DCAR and DDCAR display similar functions and are as pharmacologically potent as the parent drug.

Route of elimination

Urine (21% of dose)

Half life

~1 week for the combined drug.

ClearanceNot Available
Toxicity

Accidental acute overdosage (48 mg/day) was reported in one patient. This patient experienced orthostasis and sedation. The patient fully recovered the same day. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Cariprazine is not approved for the treatment of patients with dementia-related psychosis.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamineCariprazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.Experimental, Illicit
3,4-MethylenedioxyamphetamineCariprazine may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.Experimental, Illicit
3,4-MethylenedioxymethamphetamineCariprazine may decrease the stimulatory activities of 3,4-Methylenedioxymethamphetamine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamineCariprazine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.Experimental, Illicit
AbirateroneThe serum concentration of Cariprazine can be increased when it is combined with Abiraterone.Approved
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Cariprazine.Approved, Investigational
AmantadineThe therapeutic efficacy of Amantadine can be decreased when used in combination with Cariprazine.Approved
AmiodaroneThe metabolism of Cariprazine can be decreased when combined with Amiodarone.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Cariprazine is combined with Amisulpride.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Cariprazine.Approved
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Cariprazine.Approved
AmphetamineCariprazine may decrease the stimulatory activities of Amphetamine.Approved, Illicit
ApomorphineThe therapeutic efficacy of Apomorphine can be decreased when used in combination with Cariprazine.Approved, Investigational
AprepitantThe serum concentration of Cariprazine can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Cariprazine can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Cariprazine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Cariprazine can be decreased when combined with Atomoxetine.Approved
BenzphetamineCariprazine may decrease the stimulatory activities of Benzphetamine.Approved, Illicit
BetaxololThe metabolism of Cariprazine can be decreased when combined with Betaxolol.Approved
BexaroteneThe serum concentration of Cariprazine can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Cariprazine can be decreased when combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Cariprazine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Cariprazine can be decreased when it is combined with Bosentan.Approved, Investigational
BromocriptineThe therapeutic efficacy of Bromocriptine can be decreased when used in combination with Cariprazine.Approved, Investigational
BupropionThe metabolism of Cariprazine can be decreased when combined with Bupropion.Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Cariprazine.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Cariprazine.Approved
CarbamazepineThe metabolism of Cariprazine can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Cariprazine can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Cariprazine can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Cariprazine can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorphentermineCariprazine may decrease the stimulatory activities of Chlorphentermine.Illicit, Withdrawn
ChlorpromazineThe metabolism of Cariprazine can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Cariprazine can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Cariprazine can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Cariprazine can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Cariprazine can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Cariprazine can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Cariprazine can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Cariprazine can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Cariprazine can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Cariprazine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Cariprazine can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Cariprazine can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Cariprazine can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Cariprazine can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Cariprazine can be decreased when combined with Crizotinib.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Cariprazine.Approved
CyclosporineThe metabolism of Cariprazine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Cariprazine can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Cariprazine can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Cariprazine can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Cariprazine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Cariprazine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Cariprazine can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Cariprazine can be decreased when combined with Desipramine.Approved
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Cariprazine.Approved
DexamethasoneThe serum concentration of Cariprazine can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextroamphetamineCariprazine may decrease the stimulatory activities of Dextroamphetamine.Approved, Illicit
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Cariprazine.Approved
DiethylpropionCariprazine may decrease the stimulatory activities of Diethylpropion.Approved, Illicit
DihydroergotamineThe metabolism of Cariprazine can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Cariprazine can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Cariprazine can be decreased when combined with Diphenhydramine.Approved
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Cariprazine.Approved
DoxycyclineThe metabolism of Cariprazine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Cariprazine can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Cariprazine can be decreased when combined with Duloxetine.Approved
EfavirenzThe serum concentration of Cariprazine can be decreased when it is combined with Efavirenz.Approved, Investigational
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Cariprazine.Approved, Investigational
EliglustatThe metabolism of Cariprazine can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Cariprazine can be decreased when it is combined with Enzalutamide.Approved
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Cariprazine.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Cariprazine.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Cariprazine.Approved
ErythromycinThe metabolism of Cariprazine can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Cariprazine.Approved, Investigational
Eslicarbazepine acetateThe serum concentration of Cariprazine can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Cariprazine can be decreased when it is combined with Etravirine.Approved
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Cariprazine.Approved, Illicit, Investigational, Vet Approved
FluconazoleThe metabolism of Cariprazine can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Cariprazine can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Cariprazine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Cariprazine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Cariprazine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Cariprazine can be increased when combined with Fosphenytoin.Approved
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Cariprazine.Approved, Investigational
Fusidic AcidThe serum concentration of Cariprazine can be increased when it is combined with Fusidic Acid.Approved
HaloperidolThe metabolism of Cariprazine can be decreased when combined with Haloperidol.Approved
HydroxyamphetamineCariprazine may decrease the stimulatory activities of Hydroxyamphetamine hydrobromide.Approved
IdelalisibThe serum concentration of Cariprazine can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Cariprazine can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Cariprazine can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Cariprazine can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Cariprazine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Cariprazine.Approved
IsoniazidThe metabolism of Cariprazine can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Cariprazine can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Cariprazine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Cariprazine can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Cariprazine can be decreased when combined with Ketoconazole.Approved, Investigational
LevodopaThe therapeutic efficacy of Levodopa can be decreased when used in combination with Cariprazine.Approved
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Cariprazine.Approved
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Cariprazine.Approved, Investigational
LisdexamfetamineCariprazine may decrease the stimulatory activities of Lisdexamfetamine.Approved, Investigational
LithiumLithium may increase the neurotoxic activities of Cariprazine.Approved
LopinavirThe metabolism of Cariprazine can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Cariprazine can be decreased when combined with Lorcaserin.Approved
LovastatinThe metabolism of Cariprazine can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Cariprazine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Cariprazine can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Cariprazine can be decreased when combined with Lumefantrine.Approved
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Cariprazine.Approved
MephedroneCariprazine may decrease the stimulatory activities of Mephedrone.Investigational
MephentermineCariprazine may decrease the stimulatory activities of Mephentermine.Approved
MequitazineCariprazine may increase the arrhythmogenic activities of Mequitazine.Approved
MethadoneThe metabolism of Cariprazine can be decreased when combined with Methadone.Approved
MethamphetamineCariprazine may decrease the stimulatory activities of Methamphetamine.Approved, Illicit
MethotrimeprazineThe metabolism of Cariprazine can be decreased when combined with Methotrimeprazine.Approved
MethylphenidateThe risk or severity of adverse effects can be increased when Cariprazine is combined with Methylphenidate.Approved, Investigational
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Cariprazine.Approved, Investigational
MetoprololThe metabolism of Cariprazine can be decreased when combined with Metoprolol.Approved, Investigational
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Cariprazine.Approved
MifepristoneThe serum concentration of Cariprazine can be increased when it is combined with Mifepristone.Approved, Investigational
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Cariprazine.Approved
MirabegronThe metabolism of Cariprazine can be decreased when combined with Mirabegron.Approved
MirtazapineThe risk or severity of adverse effects can be increased when Mirtazapine is combined with Cariprazine.Approved
MitotaneThe serum concentration of Cariprazine can be decreased when it is combined with Mitotane.Approved
MMDACariprazine may decrease the stimulatory activities of MMDA.Experimental, Illicit
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Cariprazine.Approved
ModafinilThe serum concentration of Cariprazine can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Cariprazine can be decreased when it is combined with Nafcillin.Approved
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Cariprazine.Approved, Investigational
NefazodoneThe metabolism of Cariprazine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Cariprazine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Cariprazine can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Cariprazine can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Cariprazine can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Cariprazine can be decreased when combined with Nilotinib.Approved, Investigational
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Cariprazine.Approved
OlaparibThe metabolism of Cariprazine can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Cariprazine can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Cariprazine can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Cariprazine can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Cariprazine can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Cariprazine can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Cariprazine can be increased when combined with Pentobarbital.Approved, Vet Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Cariprazine.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Cariprazine.Approved
PhenobarbitalThe metabolism of Cariprazine can be increased when combined with Phenobarbital.Approved
PhentermineCariprazine may decrease the stimulatory activities of Phentermine.Approved, Illicit
PhenytoinThe metabolism of Cariprazine can be increased when combined with Phenytoin.Approved, Vet Approved
PiribedilThe therapeutic efficacy of Piribedil can be decreased when used in combination with Cariprazine.Investigational
PosaconazoleThe metabolism of Cariprazine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PramipexoleThe therapeutic efficacy of Pramipexole can be decreased when used in combination with Cariprazine.Approved, Investigational
PrimidoneThe metabolism of Cariprazine can be increased when combined with Primidone.Approved, Vet Approved
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Cariprazine.Approved
PromazineThe metabolism of Cariprazine can be decreased when combined with Promazine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Cariprazine.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Cariprazine.Approved
PseudoephedrineCariprazine may decrease the stimulatory activities of Pseudoephedrine.Approved
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Cariprazine.Approved
QuinidineThe metabolism of Cariprazine can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Cariprazine can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Cariprazine can be decreased when combined with Ranolazine.Approved, Investigational
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Cariprazine.Approved
RifabutinThe metabolism of Cariprazine can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Cariprazine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Cariprazine can be increased when combined with Rifapentine.Approved
RitobegronCariprazine may decrease the stimulatory activities of Ritobegron.Investigational
RitonavirThe metabolism of Cariprazine can be decreased when combined with Ritonavir.Approved, Investigational
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Cariprazine.Approved
RolapitantThe metabolism of Cariprazine can be decreased when combined with Rolapitant.Approved
RopiniroleThe therapeutic efficacy of Ropinirole can be decreased when used in combination with Cariprazine.Approved, Investigational
RotigotineThe therapeutic efficacy of Rotigotine can be decreased when used in combination with Cariprazine.Approved
SaquinavirThe metabolism of Cariprazine can be decreased when combined with Saquinavir.Approved, Investigational
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Cariprazine.Approved, Investigational, Vet Approved
SertralineThe metabolism of Cariprazine can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Cariprazine can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Cariprazine can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Cariprazine can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Cariprazine can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Cariprazine can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Cariprazine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulpirideThe risk or severity of adverse effects can be increased when Cariprazine is combined with Sulpiride.Approved
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Cariprazine.Approved, Investigational
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Cariprazine.Approved
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Cariprazine.Approved
TelaprevirThe metabolism of Cariprazine can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Cariprazine can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Cariprazine can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Cariprazine.Approved
ThioridazineThe metabolism of Cariprazine can be decreased when combined with Thioridazine.Withdrawn
TiclopidineThe metabolism of Cariprazine can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Cariprazine can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Cariprazine can be decreased when it is combined with Tocilizumab.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Cariprazine.Approved, Investigational
TranylcypromineThe metabolism of Cariprazine can be decreased when combined with Tranylcypromine.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Cariprazine.Approved, Investigational
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Cariprazine.Approved
VenlafaxineThe metabolism of Cariprazine can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Cariprazine can be decreased when combined with Verapamil.Approved
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Cariprazine.Approved
VoriconazoleThe metabolism of Cariprazine can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Cariprazine.Approved
ZiprasidoneThe metabolism of Cariprazine can be decreased when combined with Ziprasidone.Approved
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Cariprazine.Approved, Investigational
Food InteractionsNo interactions found.
References
Synthesis Reference

Agai-Csongor E, Domany G, Nogradi K, Galambos J, Vago I, Keseru GM, Greiner I, Laszlovszky I, Gere A, Schmidt E, Kiss B, Vastag M, Tihanyi K, Saghy K, Laszy J, Gyertyan I, Zajer-Balazs M, Gemesi L, Kapas M, Szombathelyi Z: Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors. Bioorg Med Chem Lett. 2012 May 15;22(10):3437-40. doi: 10.1016/j.bmcl.2012.03.104. Epub 2012 Apr 4. Pubmed

General References
  1. Citrome L: Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206. doi: 10.1517/17425255.2013.759211. [PubMed:23320989 ]
  2. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [PubMed:26510944 ]
External Links
ATC CodesN05AX15 — Cariprazine
AHFS Codes
  • 28:16.08.04
PDB EntriesNot Available
FDA labelDownload (525 KB)
MSDSDownload (61.7 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentPharmacokinetic Profile1
1CompletedTreatmentSchizophrenic Disorders1
2CompletedTreatmentBipolar Disorder (BD)1
2CompletedTreatmentDepression, Bipolar2
2CompletedTreatmentMajor Depressive Disorder (MDD)2
2CompletedTreatmentSchizophrenic Disorders4
2, 3CompletedTreatmentSchizophrenic Disorders5
3Active Not RecruitingTreatmentMajor Depressive Disorder (MDD)1
3CompletedPreventionSchizophrenic Disorders1
3CompletedTreatmentBipolar Disorder (BD) / Mania1
3CompletedTreatmentBipolar I Disorder1
3CompletedTreatmentBipolar I Disorder / Mania1
3CompletedTreatmentMajor Depressive Disorder (MDD)1
3CompletedTreatmentSchizophrenic Disorders3
3RecruitingTreatmentBipolar Disorder (BD) / Depressive State2
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsule, gelatin coatedOral1.5 mg/1
Capsule, gelatin coatedOral3 mg/1
Capsule, gelatin coatedOral4.5 mg/1
Capsule, gelatin coatedOral6 mg/1
KitOral
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7737142 No2007-03-272027-03-27Us
US7943621 No2008-12-162028-12-16Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0279 mg/mLALOGPS
logP4.56ALOGPS
logP4.06ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)15.68ChemAxon
pKa (Strongest Basic)7.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.82 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity117.81 m3·mol-1ChemAxon
Polarizability48.07 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentPhenylpiperazines
Alternative ParentsN-arylpiperazines / Dichlorobenzenes / Dialkylarylamines / Aniline and substituted anilines / N-alkylpiperazines / Aryl chlorides / Ureas / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
SubstituentsPhenylpiperazine / N-arylpiperazine / 1,2-dichlorobenzene / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aniline or substituted anilines / N-alkylpiperazine / Chlorobenzene / Halobenzene / Aryl halide
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonistpartial agonist
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name:
DRD3
Uniprot ID:
P35462
Uniprot Name:
D(3) dopamine receptor
Molecular Weight:
44224.335 Da
References
  1. Citrome L: Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206. doi: 10.1517/17425255.2013.759211. [PubMed:23320989 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonistpartial agonist
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Uniprot Name:
D(2) dopamine receptor
Molecular Weight:
50618.91 Da
References
  1. Citrome L: Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206. doi: 10.1517/17425255.2013.759211. [PubMed:23320989 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonistpartial agonist
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G pro...
Gene Name:
HTR1A
Uniprot ID:
P08908
Uniprot Name:
5-hydroxytryptamine receptor 1A
Molecular Weight:
46106.335 Da
References
  1. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [PubMed:26510944 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins ...
Gene Name:
HTR2B
Uniprot ID:
P41595
Uniprot Name:
5-hydroxytryptamine receptor 2B
Molecular Weight:
54297.41 Da
References
  1. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [PubMed:26510944 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
Uniprot Name:
5-hydroxytryptamine receptor 2A
Molecular Weight:
52602.58 Da
References
  1. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [PubMed:26510944 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Uniprot Name:
Histamine H1 receptor
Molecular Weight:
55783.61 Da
References
  1. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [PubMed:26510944 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
References
  1. Citrome L: Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206. doi: 10.1517/17425255.2013.759211. [PubMed:23320989 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Uniprot Name:
Cytochrome P450 2D6
Molecular Weight:
55768.94 Da
References
  1. Citrome L: Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206. doi: 10.1517/17425255.2013.759211. [PubMed:23320989 ]
Drug created on November 18, 2007 11:29 / Updated on September 01, 2017 11:26