Cariprazine
Identification
- Summary
Cariprazine is an atypical antipsychotic used to treat schizophrenia and acute manic or mixed episodes due to bipolar I disorder.
- Brand Names
- Vraylar
- Generic Name
- Cariprazine
- DrugBank Accession Number
- DB06016
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Cariprazine (DB06016)
- Weight
- Average: 427.41
Monoisotopic: 426.1953171 - Chemical Formula
- C21H32Cl2N4O
- Synonyms
- Cariprazine
- trans-N-{4-[2-[4-(2,3-dichlorophenyl)piperazine-1-yl]ethyl]cyclohexyl}-N’,N’-dimethylurea hydrochloride
- External IDs
- MP-214
- RGH-188
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.
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- Associated Conditions
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- 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.
Target Actions Organism ADopamine D3 receptor agonistpartial agonistHumans ADopamine D2 receptor agonistpartial agonistHumans A5-hydroxytryptamine receptor 1A agonistpartial agonistHumans A5-hydroxytryptamine receptor 2B antagonistHumans A5-hydroxytryptamine receptor 2A antagonistHumans AHistamine H1 receptor antagonistHumans - 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
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Cariprazine is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Cariprazine can be increased when it is combined with Abametapir. Abatacept The metabolism of Cariprazine can be increased when combined with Abatacept. Abiraterone The metabolism of Cariprazine can be decreased when combined with Abiraterone. Acebutolol The metabolism of Cariprazine can be decreased when combined with Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Cariprazine is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Cariprazine is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Cariprazine is combined with Acenocoumarol. Acetaminophen The metabolism of Cariprazine can be decreased when combined with Acetaminophen. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Cariprazine. 
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- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Product Ingredients
Ingredient UNII CAS InChI Key Cariprazine hydrochloride KQD7C255YG 1083076-69-0 GPPJWWMREQHLQT-BHQIMSFRSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Reagila Capsule 3 mg Oral Gedeon Richter 2020-12-16 Not applicable EU 
Reagila Capsule 4.5 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 3 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 4.5 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 4.5 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 3 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 6 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 4.5 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 1.5 mg Oral Gedeon Richter 2020-12-16 Not applicable EU Reagila Capsule 6 mg Oral Gedeon Richter 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Vraylar Cariprazine (1.5 mg/1) + Cariprazine (3 mg/1) Kit Oral Allergan, Inc. 2015-09-17 Not applicable US 
Vraylar Cariprazine (1.5 mg/1) + Cariprazine (3 mg/1) Kit Oral Allergan, Inc. 2015-09-17 Not applicable US
Categories
- ATC Codes
- N05AX15 — Cariprazine
- Drug Categories
- Agents that produce hypertension
- Antidepressive Agents
- Antipsychotic Agents
- Antipsychotic Agents (Second Generation [Atypical])
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Histamine Antagonists
- Histamine H1 Antagonists
- Nervous System
- Neurotoxic agents
- Psycholeptics
- Psychotropic Drugs
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Agonists
- Serotonin Receptor Antagonists
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- 1,2-dichlorobenzene / Amine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- F6RJL8B278
- CAS number
- 839712-12-8
- 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
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
- 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. [Article]
- McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
- External Links
- KEGG Drug
- D09997
- PubChem Compound
- 11154555
- PubChem Substance
- 310264859
- ChemSpider
- 25999972
- BindingDB
- 50443101
- 1667655
- ChEBI
- 90933
- ChEMBL
- CHEMBL2028019
- ZINC
- ZINC000100907004
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cariprazine
- FDA label
- Download (525 KB)
- MSDS
- Download (61.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Treatment Attention Deficit Hyperactivity Disorder (ADHD) / Attention Deficit/Hyperactivity Disorder 1 3 Active Not Recruiting Treatment Schizophrenia 2 3 Completed Prevention Schizophrenia 1 3 Completed Treatment Bipolar 1 Disorder 1 3 Completed Treatment Bipolar 1 Disorder / Mania 1 3 Completed Treatment Bipolar Disorder (BD) / Depression 2 3 Completed Treatment Bipolar Disorder (BD) / Mania 1 3 Completed Treatment Major Depressive Disorder (MDD) 2 3 Completed Treatment Schizophrenia 3 3 Not Yet Recruiting Treatment Bipolar 1 Disorder / Cognitive Impairments 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 1.5 mg Capsule Oral 3 mg Capsule Oral 4.5 mg Capsule Oral 6 mg Capsule Oral Capsule, gelatin coated Oral 1.5 mg/1 Capsule, gelatin coated Oral 3 mg/1 Capsule, gelatin coated Oral 4.5 mg/1 Capsule, gelatin coated Oral 6 mg/1 Kit Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7737142 No 2010-06-15 2027-03-27 US US7943621 No 2011-05-17 2028-12-16 US USRE47350 No 2019-04-16 2029-07-16 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0279 mg/mL ALOGPS logP 4.56 ALOGPS logP 4.06 ChemAxon logS -4.2 ALOGPS pKa (Strongest Acidic) 15.68 ChemAxon pKa (Strongest Basic) 7.91 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 38.82 Å2 ChemAxon Rotatable Bond Count 5 ChemAxon Refractivity 117.81 m3·mol-1 ChemAxon Polarizability 48.07 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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...
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
Drug created on November 18, 2007 18:29 / Updated on May 07, 2021 21:39