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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H32Cl2N4O
Molecular Weight 427.411
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARIPRAZINE

SMILES

CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(CC2)C3=C(Cl)C(Cl)=CC=C3)CC1

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

Molecular Formula C21H32Cl2N4O
Molecular Weight 427.411
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

1.44244802E12
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

1.44244802E12
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 (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
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 (mean)
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)
n = 169
Health Status: unhealthy
Condition: bipolar I disorder
Age Group: 41,2 years (range: 18-65 years)
Sex: M+F
Population Size: 169
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
n = 17
Health Status: unhealthy
Condition: dementia related psychosis
Age Group: Elderly
Population Size: 17
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
Health Status: unhealthy
Condition: bipolar mania
Sources:
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 (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Musculoskeletal stiffness 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Parkinsonism 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Restlessness 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Salivary hypersecretion 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Tremor 0.2%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Extrapyramidal disorder 0.3%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Akathisia 0.9%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Bilirubin increased 1 patient
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
ALT increased 2 patients
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
AST increased 2 patients
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Psychotic disorder 2%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Schizophrenia aggravated 2.7%
Disc. AE
5.7 mg 1 times / day steady, oral (mean)
Recommended
Dose: 5.7 mg, 1 times / day
Route: oral
Route: steady
Dose: 5.7 mg, 1 times / day
Sources:
unhealthy, 39.1 years
n = 586
Health Status: unhealthy
Condition: schizophrenia
Age Group: 39.1 years
Sex: M+F
Population Size: 586
Sources:
Akathisia Disc. AE
12 mg 1 times / day steady, oral (mean)
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)
n = 169
Health Status: unhealthy
Condition: bipolar I disorder
Age Group: 41,2 years (range: 18-65 years)
Sex: M+F
Population Size: 169
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
n = 17
Health Status: unhealthy
Condition: dementia related psychosis
Age Group: Elderly
Population Size: 17
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
Health Status: unhealthy
Condition: bipolar mania
Sources:
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: 29.0
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: 29.0
Tox targets
PubMed

PubMed

TitleDatePubMed
Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability.
2013 Feb
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 00:42:14 UTC 2023
Edited
by admin
on Sat Dec 16 00:42:14 UTC 2023
Record UNII
F6RJL8B278
Record Status Validated (UNII)
Record Version
  • Download
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 [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
Cariprazine [WHO-DD]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175430
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
WHO-ATC N05AX15
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
Code System Code Type Description
LACTMED
Cariprazine
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
SMS_ID
100000128115
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
MESH
C533287
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
PUBCHEM
11154555
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
EPA CompTox
DTXSID80232867
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
FDA UNII
F6RJL8B278
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
NCI_THESAURUS
C169826
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
CAS
839712-12-8
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
EVMPD
SUB34830
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
WIKIPEDIA
Cariprazine
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
DAILYMED
F6RJL8B278
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
IUPHAR
7671
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
MERCK INDEX
m11853
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
USAN
YY-06
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
INN
8920
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
RXCUI
1667655
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY RxNorm
HSDB
8310
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
ChEMBL
CHEMBL2028019
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
CHEBI
90933
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
DRUG BANK
DB06016
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
DRUG CENTRAL
5037
Created by admin on Sat Dec 16 00:42:14 UTC 2023 , Edited by admin on Sat Dec 16 00:42:14 UTC 2023
PRIMARY
Related Record Type Details
TARGET->WEAK INHIBITOR
Ki
TARGET->PARTIAL AGONIST
Ki
TARGET->PARTIAL AGONIST
Most of the clinically used antipsychotics display fairly high affinity for D3 receptors in vitro, they lack significant D3 receptor binding in vivo. They also do not occupy D3 receptors in schizophrenic patients at clinically-relevant doses, despite having significant and expected D2 receptor occupancy. The lack of in vivo D3 receptor occupancy of currently used antipsychotics may be due to their inability to displace endogenous DA from these sites; especially since DA has approximately 20- fold higher affinity for D3 vs D2 receptors and D3 (but not D2) receptors exist predominantly in a high affinity state for DA”
Ki
TARGET->WEAK INHIBITOR
Ki
SALT/SOLVATE -> PARENT
TARGET->PARTIAL AGONIST
Ki
TARGET -> INHIBITOR
Ki
TRANSPORTER -> NON-INHIBITOR
Ki
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE ACTIVE -> PARENT
minor enzyme involved in metabolism
MINOR
PLASMA
METABOLITE ACTIVE -> PARENT
activity same as CARIPRAZINE; steady state plasma level 400% of CARIPRAZINE
MAJOR
PLASMA
METABOLITE ACTIVE -> PARENT
MINOR
PLASMA
METABOLITE ACTIVE -> PARENT
activity same as CARIPRAZINE, steady state level 30% of CARIPRAZINE
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC