U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H32Cl2N4O
Molecular Weight 427.4117
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARIPRAZINE

SMILES

CN(C)C(=N[C@@]1([H])CC[C@@]([H])(CC1)CCN2CCN(CC2)c3cccc(c3Cl)Cl)O

InChI

InChIKey=KPWSJANDNDDRMB-QAQDUYKDSA-N
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-

HIDE SMILES / InChI
Cariprazine is an antipsychotic approved by FDA for the treatment of schizophrenia and bipolar I disorder. The drug has a unique clinical action which is explained by its ability to act on dopamine D3 receptors. Pharmacology studies revealed that cariprazine is a dual partial agonist of dopamine D2 and D3 receptors as well as serotonin 5HT1a, 2a and 2b receptors.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VRAYLAR

Approved Use

VRAYLAR is indicated for the treatment of schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder.

Launch Date

1442448000000
Primary
VRAYLAR

Approved Use

VRAYLAR is indicated for the treatment of schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder.

Launch Date

1442448000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.2 ng/mL
3 mg 1 times / day multiple, oral
dose: 3 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
22.7 ng/mL
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
28.8 ng/mL
9 mg 1 times / day multiple, oral
dose: 9 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
156 ng × h/mL
3 mg 1 times / day multiple, oral
dose: 3 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
358 ng × h/mL
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
466 ng × h/mL
9 mg 1 times / day multiple, oral
dose: 9 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
68.4 h
3 mg 1 times / day multiple, oral
dose: 3 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
44.3 h
6 mg 1 times / day multiple, oral
dose: 6 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
31.6 h
9 mg 1 times / day multiple, oral
dose: 9 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
9%
unknown, unknown
CARIPRAZINE HYDROCHLORIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Disc. AE: Schizophrenia aggravated, Psychotic disorder...
AEs leading to
discontinuation/dose reduction:
Schizophrenia aggravated (2.7%)
Psychotic disorder (2%)
ALT increased (2 patients)
AST increased (2 patients)
Bilirubin increased (1 patient)
Akathisia (0.9%)
Extrapyramidal disorder (0.3%)
Restlessness (0.2%)
Dystonia (0.2%)
Parkinsonism (0.2%)
Salivary hypersecretion (0.2%)
Tremor (0.2%)
Musculoskeletal stiffness (0.2%)
Sources:
12 mg 1 times / day steady, oral
Highest studied dose
Dose: 12 mg, 1 times / day
Route: oral
Route: steady
Dose: 12 mg, 1 times / day
Sources:
unhealthy, 41,2 years (range: 18-65 years)
Health Status: unhealthy
Age Group: 41,2 years (range: 18-65 years)
Sex: M+F
Sources:
Disc. AE: Akathisia...
AEs leading to
discontinuation/dose reduction:
Akathisia
Sources:
6 mg 1 times / day steady, oral
Recommended
Dose: 6 mg, 1 times / day
Route: oral
Route: steady
Dose: 6 mg, 1 times / day
Sources:
unhealthy, Elderly
Health Status: unhealthy
Age Group: Elderly
Sources:
Other AEs: Adverse event...
3 mg 1 times / day steady, oral
Recommended
Dose: 3 mg, 1 times / day
Route: oral
Route: steady
Dose: 3 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Akathisia...
AEs leading to
discontinuation/dose reduction:
Akathisia (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Dystonia 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Musculoskeletal stiffness 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Parkinsonism 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Restlessness 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Salivary hypersecretion 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Tremor 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Extrapyramidal disorder 0.3%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Akathisia 0.9%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Bilirubin increased 1 patient
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
ALT increased 2 patients
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
AST increased 2 patients
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Psychotic disorder 2%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Schizophrenia aggravated 2.7%
Disc. AE
5.7 mg 1 times / day steady, oral
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
Health Status: unhealthy
Age Group: 39.1 years
Sex: M+F
Sources:
Akathisia Disc. AE
12 mg 1 times / day steady, oral
Highest studied dose
Dose: 12 mg, 1 times / day
Route: oral
Route: steady
Dose: 12 mg, 1 times / day
Sources:
unhealthy, 41,2 years (range: 18-65 years)
Health Status: unhealthy
Age Group: 41,2 years (range: 18-65 years)
Sex: M+F
Sources:
Adverse event grade 5
6 mg 1 times / day steady, oral
Recommended
Dose: 6 mg, 1 times / day
Route: oral
Route: steady
Dose: 6 mg, 1 times / day
Sources:
unhealthy, Elderly
Health Status: unhealthy
Age Group: Elderly
Sources:
Akathisia 2%
Disc. AE
3 mg 1 times / day steady, oral
Recommended
Dose: 3 mg, 1 times / day
Route: oral
Route: steady
Dose: 3 mg, 1 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
weak
weak
weak
weak
weak
weak
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes (co-administration study)
Comment: In vivo data showed that a strong CYP3A4 inhibitor (i.e., ketoconazole) increased the total effective exposure after cariprazine administration by about 100% (study RGH-PK-07).
Page: 29
yes
yes (pharmacogenomic study)
Comment: Based on a population PK analysis, steady-state AUC0-24 of DDCAR in poor metabolizers of CYP2D6 was about 16% higher than in extensive metabolizers.
Page: 29
Tox targets
PubMed

PubMed

TitleDatePubMed
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.
2010 Apr
Cariprazine, an orally active D2/D3 receptor antagonist, for the potential treatment of schizophrenia, bipolar mania and depression.
2010 Jul
Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors.
2012 May 15
Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability.
2013 Feb
Cariprazine: First Global Approval.
2015 Nov
Patents

Sample Use Guides

The recommended dose is from 1.5 mg to 6 mg/day (schizophrenia) and 3 mg to 6 mg/day (bipolar mania).
Route of Administration: Oral
Rat striatal and hippocampal membrane preparation were treated with a range of cariprazine concentrations from 0.1 nM to 0.1 mM to study [35S]GTPgammaS binding.
Name Type Language
CARIPRAZINE
DASH   INN   USAN   WHO-DD  
USAN   INN  
Official Name English
CARIPRAZINE [USAN]
Common Name English
FRI-7000188
Common Name English
CARIPRAZINE [WHO-DD]
Common Name English
CARIPRAZINE [INN]
Common Name English
CARIPRAZINE [MI]
Common Name English
GED-129
Code English
3-(TRANS-4-(2-(4-(2,3-DICHLOROPHENYL)PIPERAZIN-1-YL)ETHYL)CYCLOHEXYL)-1,1-DIMETHYLUREA
Systematic Name English
MP-214
Code English
RGH-188
Code English
Classification Tree Code System Code
NDF-RT N0000175430
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
WHO-ATC N05AX15
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
Code System Code Type Description
LACTMED
Cariprazine
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
MESH
C533287
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
PUBCHEM
11154555
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
EPA CompTox
839712-12-8
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
FDA UNII
F6RJL8B278
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
NCI_THESAURUS
C169826
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
CAS
839712-12-8
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
EVMPD
SUB34830
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
WIKIPEDIA
Cariprazine
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
IUPHAR
7671
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
MERCK INDEX
M11853
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
INN
8920
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
RXCUI
1667655
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY RxNorm
HSDB
8310
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL2028019
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
DRUG BANK
DB06016
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY
DRUG CENTRAL
5037
Created by admin on Sat Jun 26 09:29:48 UTC 2021 , Edited by admin on Sat Jun 26 09:29:48 UTC 2021
PRIMARY