Identification

Name
Cariprazine
Accession Number
DB06016
Type
Small Molecule
Groups
Approved, Investigational
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 Key
Cariprazine hydrochlorideKQD7C255YG1083076-69-0GPPJWWMREQHLQT-BHQIMSFRSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VraylarCapsule, gelatin coated1.5 mg/1OralAllergan2015-09-17Not applicableUs
VraylarCapsule, gelatin coated4.5 mg/1OralAllergan2015-09-17Not applicableUs
VraylarKitOralAllergan2015-09-17Not applicableUs
VraylarCapsule, gelatin coated3 mg/1OralAllergan2015-09-17Not applicableUs
VraylarCapsule, gelatin coated6 mg/1OralAllergan2015-09-17Not applicableUs
Categories
UNII
F6RJL8B278
CAS number
839712-12-8
Weight
Average: 427.41
Monoisotopic: 426.1953171
Chemical Formula
C21H32Cl2N4O
InChI Key
KPWSJANDNDDRMB-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[C@H]1CC[C@H](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.

Associated Conditions
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.

TargetActionsOrganism
AD(3) dopamine receptor
agonist
partial agonist
Human
AD(2) dopamine receptor
agonist
partial agonist
Human
A5-hydroxytryptamine receptor 1A
agonist
partial agonist
Human
A5-hydroxytryptamine receptor 2B
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
AHistamine H1 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not 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.

Clearance
Not 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
Pathways
Not 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
2,5-Dimethoxy-4-ethylthioamphetamineCariprazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.Experimental
3,4-MethylenedioxyamphetamineCariprazine may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamineCariprazine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.Experimental, Illicit
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe metabolism of Cariprazine can be decreased when combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.Experimental
AbirateroneThe serum concentration of Cariprazine can be increased when it is combined with Abiraterone.Approved
Acetyl sulfisoxazoleThe metabolism of Cariprazine can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet 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
AmisulprideCariprazine may increase the antipsychotic activities of 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
AmphetamineThe metabolism of Cariprazine can be decreased when combined with Amphetamine.Approved, Illicit, Investigational
ApalutamideThe serum concentration of Cariprazine can be decreased when it is combined with Apalutamide.Approved, Investigational
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
BenmoxinThe metabolism of Cariprazine can be decreased when combined with Benmoxin.Withdrawn
BenzphetamineCariprazine may decrease the stimulatory activities of Benzphetamine.Approved, Illicit
Benzylpenicilloyl PolylysineCariprazine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Cariprazine.Approved, Investigational
BetaxololThe metabolism of Cariprazine can be decreased when combined with Betaxolol.Approved, Investigational
BoceprevirThe metabolism of Cariprazine can be decreased when combined with Boceprevir.Approved, 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
BrofaromineThe metabolism of Cariprazine can be decreased when combined with Brofaromine.Experimental
BromocriptineBromocriptine may increase the vasoconstricting activities of 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
CabergolineCabergoline may increase the vasoconstricting activities of Cariprazine.Approved
CarbamazepineThe metabolism of Cariprazine can be increased when combined with Carbamazepine.Approved, Investigational
CaroxazoneThe metabolism of Cariprazine can be decreased when combined with Caroxazone.Withdrawn
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, Investigational, Vet Approved
ChlorphentermineCariprazine may decrease the stimulatory activities of Chlorphentermine.Illicit, Withdrawn
ChlorpromazineThe metabolism of Cariprazine can be decreased when combined with Chlorpromazine.Approved, Investigational, 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, Investigational
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, Investigational
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, Investigational, 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 Conivaptan can be increased when it is combined with Cariprazine.Approved, Investigational
CrizotinibThe metabolism of Cariprazine can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Cariprazine can be decreased when combined with Curcumin.Approved, Investigational
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, Investigational
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, Investigational
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Cariprazine.Approved, Investigational
DeutetrabenazineThe risk or severity of adverse effects can be increased when Cariprazine is combined with Deutetrabenazine.Approved, Investigational
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
DihydroergotamineDihydroergotamine may increase the vasoconstricting activities of Cariprazine.Approved, Investigational
DiltiazemThe metabolism of Cariprazine can be decreased when combined with Diltiazem.Approved, Investigational
DiphenhydramineThe metabolism of Cariprazine can be decreased when combined with Diphenhydramine.Approved, Investigational
DosulepinThe metabolism of Cariprazine can be decreased when combined with Dosulepin.Approved
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Cariprazine.Approved, Investigational
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
DroxidopaCariprazine may increase the hypertensive activities of Droxidopa.Approved, Investigational
DuloxetineThe metabolism of Cariprazine can be decreased when combined with Duloxetine.Approved
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 mesylateErgoloid mesylate may increase the vasoconstricting activities of Cariprazine.Approved
ErgonovineErgonovine may increase the vasoconstricting activities of Cariprazine.Approved
ErgotamineErgotamine may increase the vasoconstricting activities of Cariprazine.Approved
ErythromycinThe metabolism of Cariprazine can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Cariprazine.Approved, Investigational
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, Investigational
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, Investigational
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Cariprazine.Approved, Investigational
FurazolidoneThe metabolism of Cariprazine can be decreased when combined with Furazolidone.Approved, Investigational, Vet Approved
Fusidic AcidThe serum concentration of Cariprazine can be increased when it is combined with Fusidic Acid.Approved, Investigational
GepefrineCariprazine may decrease the stimulatory activities of Gepefrine.Experimental
HaloperidolThe metabolism of Cariprazine can be decreased when combined with Haloperidol.Approved
HarmalineThe metabolism of Cariprazine can be decreased when combined with Harmaline.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Cariprazine.Approved, Investigational
HydracarbazineThe metabolism of Cariprazine can be decreased when combined with Hydracarbazine.Experimental
HydroxyamphetamineCariprazine may decrease the stimulatory activities of Hydroxyamphetamine.Approved
IdelalisibThe metabolism of Cariprazine can be decreased when 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
Iofetamine I-123Cariprazine may decrease the stimulatory activities of Iofetamine I-123.Approved
IproclozideThe metabolism of Cariprazine can be decreased when combined with Iproclozide.Withdrawn
IproniazidThe metabolism of Cariprazine can be decreased when combined with Iproniazid.Withdrawn
IsavuconazoleThe serum concentration of Cariprazine can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Cariprazine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidThe metabolism of Cariprazine can be decreased when combined with Isocarboxazid.Approved
IsoniazidThe metabolism of Cariprazine can be decreased when combined with Isoniazid.Approved, Investigational
IsradipineThe metabolism of Cariprazine can be decreased when combined with Isradipine.Approved, Investigational
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
LamotrigineThe risk or severity of adverse effects can be increased when Lamotrigine is combined with Cariprazine.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, Investigational
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
LorpiprazoleThe serum concentration of Cariprazine can be increased when it is combined with Lorpiprazole.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
ManidipineThe metabolism of Cariprazine can be decreased when combined with Manidipine.Approved, Investigational
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Cariprazine.Approved, Investigational
MebanazineThe metabolism of Cariprazine can be decreased when combined with Mebanazine.Withdrawn
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, Investigational
MethoxyphenamineCariprazine may decrease the stimulatory activities of Methoxyphenamine.Experimental
Methylene blueThe metabolism of Cariprazine can be decreased when combined with Methylene blue.Approved, Investigational
MethylergometrineMethylergometrine may increase the vasoconstricting activities of Cariprazine.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
MidomafetamineCariprazine may decrease the stimulatory activities of Midomafetamine.Experimental, Illicit, Investigational
MidostaurinThe metabolism of Cariprazine can be decreased when combined with Midostaurin.Approved, Investigational
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, Investigational
MinaprineThe metabolism of Cariprazine can be decreased when combined with Minaprine.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 metabolism of Cariprazine can be decreased when combined with Moclobemide.Approved, Investigational
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, Investigational
NevirapineThe metabolism of Cariprazine can be increased when combined with Nevirapine.Approved
NialamideThe metabolism of Cariprazine can be decreased when combined with Nialamide.Withdrawn
NicardipineThe metabolism of Cariprazine can be decreased when combined with Nicardipine.Approved, Investigational
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
OctamoxinThe metabolism of Cariprazine can be decreased when combined with Octamoxin.Withdrawn
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, Investigational
PanobinostatThe serum concentration of Cariprazine can be increased when it is combined with Panobinostat.Approved, Investigational
PargylineThe metabolism of Cariprazine can be decreased when combined with Pargyline.Approved
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, Investigational, Vet Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Cariprazine.Approved
PhenelzineThe metabolism of Cariprazine can be decreased when combined with Phenelzine.Approved
PheniprazineThe metabolism of Cariprazine can be decreased when combined with Pheniprazine.Withdrawn
PhenobarbitalThe metabolism of Cariprazine can be increased when combined with Phenobarbital.Approved, Investigational
PhenoxypropazineThe metabolism of Cariprazine can be decreased when combined with Phenoxypropazine.Withdrawn
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
PirlindoleThe metabolism of Cariprazine can be decreased when combined with Pirlindole.Approved
PitolisantThe serum concentration of Cariprazine can be decreased when it is combined with Pitolisant.Approved, Investigational
PivhydrazineThe metabolism of Cariprazine can be decreased when combined with Pivhydrazine.Withdrawn
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
ProcaineThe metabolism of Cariprazine can be decreased when combined with Procaine.Approved, Investigational, Vet Approved
ProcarbazineThe metabolism of Cariprazine can be decreased when combined with Procarbazine.Approved, Investigational
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, Investigational
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, Investigational
QuinidineThe metabolism of Cariprazine can be decreased when combined with Quinidine.Approved, Investigational
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 metabolism of Cariprazine can be decreased when combined with Rasagiline.Approved
RifabutinThe metabolism of Cariprazine can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Cariprazine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Cariprazine can be increased when combined with Rifapentine.Approved, Investigational
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, Investigational
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
RucaparibThe metabolism of Cariprazine can be decreased when combined with Rucaparib.Approved, Investigational
SafrazineThe metabolism of Cariprazine can be decreased when combined with Safrazine.Withdrawn
SaquinavirThe metabolism of Cariprazine can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Cariprazine can be decreased when used in combination with Sarilumab.Approved, Investigational
SelegilineThe metabolism of Cariprazine can be decreased when combined with Selegiline.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, Investigational
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.Approved, Investigational, 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
SulpirideCariprazine may increase the antipsychotic activities of Sulpiride.Approved, Investigational
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.Approved, 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, Investigational
ThioridazineThe metabolism of Cariprazine can be decreased when combined with Thioridazine.Approved, 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
ToloxatoneThe metabolism of Cariprazine can be decreased when combined with Toloxatone.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, Investigational
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
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib 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, Investigational
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 Interactions
No 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
KEGG Drug
D09997
PubChem Compound
11154555
PubChem Substance
310264859
ChemSpider
25999972
BindingDB
50443101
ChEBI
90933
ChEMBL
CHEMBL2028019
Drugs.com
Drugs.com Drug Page
Wikipedia
Cariprazine
ATC Codes
N05AX15 — Cariprazine
FDA label
Download (525 KB)
MSDS
Download (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
2RecruitingTreatmentCocaine Use Disorders1
2, 3CompletedTreatmentSchizophrenic Disorders5
3CompletedPreventionSchizophrenic Disorders1
3CompletedTreatmentBipolar Disorder (BD) / Depression2
3CompletedTreatmentBipolar Disorder (BD) / Mania1
3CompletedTreatmentBipolar I Disorder1
3CompletedTreatmentBipolar I Disorder / Mania1
3CompletedTreatmentMajor Depressive Disorder (MDD)2
3CompletedTreatmentSchizophrenic Disorders3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not 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
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7737142No2007-03-272027-03-27Us
US7943621No2008-12-162028-12-16Us

Properties

State
Solid
Experimental Properties
Not 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 features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Dichlorobenzenes / Dialkylarylamines / Aniline and substituted anilines / N-alkylpiperazines / Aryl chlorides / Ureas / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Phenylpiperazine / N-arylpiperazine / 1,2-dichlorobenzene / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aniline or substituted anilines / N-alkylpiperazine / Chlorobenzene / Halobenzene / Aryl halide
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
Partial 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
Agonist
Partial 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
Agonist
Partial 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...
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...
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-iodop...
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 catecholamin...
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 react...
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...
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 June 02, 2018 09:36