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
SMILES
CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(CC2)C3=CC=CC(Cl)=C3Cl)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-
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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956157 |
0.49 nM [Ki] | ||
Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956157 |
0.085 nM [Ki] | ||
Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956157 |
2.6 nM [Ki] | ||
Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956157 |
18.8 nM [Ki] | ||
Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26956157 |
0.58 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VRAYLAR Approved UseVRAYLAR is indicated for the treatment of schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder. Launch Date2015 |
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Primary | VRAYLAR Approved UseVRAYLAR is indicated for the treatment of schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder. Launch Date2015 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
156 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
68.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26834462 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9% |
unknown, unknown |
CARIPRAZINE HYDROCHLORIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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%) Sources: 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%) |
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... Other AEs: Adverse event (grade 5) Sources: |
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 Sources: |
Disc. AE: Akathisia... AEs leading to discontinuation/dose reduction: Akathisia (2%) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 Health Status: unhealthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical 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). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204370Orig1Orig2s000ClinPharmR.pdf#page=29 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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204370Orig1Orig2s000ClinPharmR.pdf#page=29 Page: 29.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204370Orig1Orig2s000PharmR.pdf#page=473 Page: 473.0 |
||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204370Orig1Orig2s000PharmR.pdf#page=473 Page: 473.0 |
||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204370Orig1Orig2s000PharmR.pdf#page=473 Page: 473.0 |
PubMed
Title | Date | PubMed |
---|---|---|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20093397
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
Edited
Mon Mar 31 20:39:26 GMT 2025
by
admin
on
Mon Mar 31 20:39:26 GMT 2025
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Record UNII |
F6RJL8B278
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Record Status |
Validated (UNII)
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N0000175430
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WHO-ATC |
N05AX15
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Cariprazine
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100000128115
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C533287
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F6RJL8B278
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C169826
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SUB34830
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Cariprazine
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8310
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CHEMBL2028019
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90933
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Related Record | Type | Details | ||
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TARGET->WEAK INHIBITOR |
Ki
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TARGET->PARTIAL AGONIST |
Ki
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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
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TARGET->WEAK INHIBITOR |
Ki
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SALT/SOLVATE -> PARENT | |||
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TARGET->PARTIAL AGONIST |
Ki
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TARGET -> INHIBITOR |
Ki
|
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TRANSPORTER -> NON-INHIBITOR |
Ki
|
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE ACTIVE -> PARENT |
minor enzyme involved in metabolism
MINOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
activity same as CARIPRAZINE; steady state plasma level 400% of CARIPRAZINE
MAJOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
MINOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
activity same as CARIPRAZINE, steady state level 30% of CARIPRAZINE
MAJOR
PLASMA
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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