NAV

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 atypical antipsychotic agent and a piperazine derivative that was first developed in Hungary.6 It works as a partial agonist at central dopamine D2, dopamine D3, and serotonin 5-HT1A receptors and as an antagonist at serotonin 5-HT2A receptors.9 Cariprazine has been investigated in a variety of psychiatric disorders, including schizophrenia, bipolar disorders, and major depressive disorder. Cariprazine gained its first global approval in the US in September 2015 2 and was later approved by Health Canada in April 2022.10 It is currently used to treat schizophrenia, and manic or mixed episodes and depressive episodes associated with bipolar I disorder.9

Type
Small Molecule
Groups
Approved, Investigational
Structure
Similar Structures
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
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Pharmacology

Indication

Cariprazine is indicated for the treatment of schizophrenia in adults to manage both positive and negative symptoms. It is also indicated to monotherapy for acute management of manic or mixed episodes associated with bipolar I disorder (bipolar mania) in adults, and acute management of depressive episodes associated with bipolar I disorder (bipolar depression) in adults.11,9

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAcute depressive episode•••••••••••••••••
Management ofBipolar disorder with manic or mixed episodes•••••••••••••••••
Management ofSchizophrenia•••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Cariprazine is an antipsychotic agent. In clinical trials, it reduced positive and negative symptoms in patients with schizophrenia and acute mania in patients with bipolar I disorder. In animal models, cariprazine showed therapeutic benefits against cognitive deficits, mania, and catalepsy.2 In a meta-analysis study, cariprazine was shown to improve anxiety and depressed mood in patients with psychosis.3

As cariprazine is a partial agonist at dopamine D2 and D3 receptors, it produces an apparent lower blockade level than other antipsychotic agents that block dopamine receptors. This receptor binding profile is advantageous as dopamine receptor blockade is associated with extrapyramidal symptoms as side effects. Partial agonism would allow the dopamine receptor to be stimulated even at maximal receptor occupancy by the drug.6 Antagonism at 5-HT1A 6 and 5-HT2A receptors by cariprazine can increase dopaminergic neurotransmission in the nigrostriatal pathway, thereby further reducing the risk of extrapyramidal symptoms.3 However, cariprazine is still associated with a risk of akathisia, extrapyramidal disorder, restlessness, and tremor.2,9

Mechanism of action

While recent research points to the involvement of multiple neurotransmitters in the development and maintenance of schizophrenia and bipolar disorders, the dopamine hypothesis has been and continues to be a key theory in understanding the pathophysiology of these psychiatric disorders. Dopamine is a neurotransmitter that plays several important roles in cells, and most importantly, it is a crucial neurotransmitter involved in reward processing and motivation. The nigrostriatal, mesolimbic, and mesocortical systems consist of dopaminergic projections. The dopamine hypothesis states that dopaminergic aberrations are observed in schizophrenia and bipolar disorders.7,8 For example, hyperactive dopamine D2 receptor activity has been associated with positive symptoms of schizophrenia, such as hallucinations and delusions. On the other hand, alterations in dopamine D3 receptors may be involved in producing negative symptoms of schizophrenia.7 It was stated that hyperdopaminergia, caused by elevations in D2/3 receptor availability and a hyperactive reward processing network, underlies the development of mania in bipolar disorder.8

The exact mechanism of action of cariprazine is not fully elucidated. Cariprazine potently binds to both of these receptors, more preferably to D3 receptors with higher affinity.2 Preclinical studies suggest that D3 receptor blockade is associated with exerting pro-cognitive and antidepressant effects and attenuating negative symptoms in schizophrenia.5 This unique mechanism of action differs from that of other antipsychotic agents that mostly target D2 and 5-HT2A receptors.3 Cariprazine is also a partial agonist at 5-HT1A receptors, an antagonist at 5-HT2B and 5-HT2A receptors, an antagonist at histamine H1 receptors. It also binds to 5-HT2C, alpha (α)-1A adrenergic, and alpha (α)-1B adrenergic receptors with low affinity.2,5

TargetActionsOrganism
UDopamine D3 receptor
partial agonist
Humans
UDopamine D2 receptor
partial agonist
Humans
U5-hydroxytryptamine receptor 1A
partial agonist
Humans
U5-hydroxytryptamine receptor 2B
antagonist
Humans
U5-hydroxytryptamine receptor 2A
antagonist
Humans
UHistamine H1 receptor
antagonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
Absorption

The most clinically relevant drug concentration equates to the combined systemic concentration of cariprazine plus desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), the two main pharmacologically active metabolites of cariprazine.2 After single dose administration of cariprazine, the peak plasma cariprazine concentration occurred in approximately three to six hours.9 In healthy volunteers, the Tmax following oral administration was 3.6 hours for cariprazine, 6.5 hours for DCAR, and 18.1 hours for DDCAR. The steady-state was reached dose-proportionally within three weeks for cariprazine, DCAR, and DDCAR in patients with schizophrenia.2

Administration of a single dose of 1.5 mg cariprazine capsule with a high-fat meal did not significantly affect the Cmax and AUC of cariprazine or its metabolite, desmethyl cariprazine (DCAR).9

Volume of distribution

Not Available

Protein binding

Cariprazine and its major active metabolites are highly bound (91 to 97%) to plasma proteins.9

Metabolism

Cariprazine is extensively metabolized by CYP3A4 and, to a lesser extent, by CYP2D6 to form two major metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). DCAR and DDCAR are pharmacologically active metabolites with in vitro receptor binding profiles similar to the parent drug. DCAR is further metabolized into DDCAR by CYP3A4 and CYP2D6. DDCAR can be metabolized by CYP3A4 to form a hydroxylated metabolite.1,2,9

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Route of elimination

Following administration of 12.5 mg/day cariprazine to patients with schizophrenia for 27 days, about 21% of the daily dose was found in urine, with approximately 1.2% of the daily dose being excreted in urine as unchanged parent drug.9

Half-life

Cariprazine and its active metabolites have long half lives.5 Terminal half-lives of cariprazine, DCAR, and DDCAR ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. The effective half-life, calculated from time to steady state, or the functional half-life of total active moieties was approximately one week.4

Clearance

Not Available

Adverse Effects
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Toxicity

In pre-marketing clinical trials, an accidental acute overdosage (48 mg/day) was reported in one patient who experienced orthostasis and sedation. The patient fully recovered the same day. As there are no specific antidotes for cariprazine, supportive care, including close medical supervision and monitoring, is advised to manage overdose. The possibility of multiple drug involvement should also be considered.9

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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.
DrugInteraction
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1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Cariprazine is combined with 1,2-Benzodiazepine.
AbametapirThe serum concentration of Cariprazine can be increased when it is combined with Abametapir.
AcebutololCariprazine may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Cariprazine is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Cariprazine is combined with Acemetacin.
Food Interactions
  • Avoid excessive or chronic alcohol consumption. Given the primary central nervous system effects of cariprazine, cariprazine should be used with caution in combination with alcohol.
  • Avoid grapefruit products. Grapefruit is a known CYP3A4 inhibitor. It may increase drug levels and elevate the risk of drug adverse effects.
  • Avoid St. John's Wort. St John’s Wort is a known CYP3A4 inducer. It may significantly decrease drug exposure and alter drug efficacy.
  • Take with or without food. A high-fat, high-calorie meal may delay Tmax, but food generally has no significant effect on drug exposure.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Cariprazine hydrochlorideKQD7C255YG1083076-69-0GPPJWWMREQHLQT-BHQIMSFRSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ReagilaCapsule3 mgOralGedeon Richter2020-12-16Not applicableEU flag
ReagilaCapsule6 mgOralGedeon Richter2020-12-16Not applicableEU flag
ReagilaCapsule1.5 mgOralGedeon Richter2020-12-16Not applicableEU flag
ReagilaCapsule4.5 mgOralGedeon Richter2020-12-16Not applicableEU flag
ReagilaCapsule1.5 mgOralGedeon Richter2020-12-16Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
VraylarCariprazine (1.5 mg/1) + Cariprazine (3 mg/1)KitOralAllergan, Inc.2015-09-172024-05-31US flag
VraylarCariprazine (1.5 mg/1) + Cariprazine (3 mg/1)KitOralAllergan, Inc.2015-09-172024-05-31US flag

Categories

ATC Codes
N05AX15 — Cariprazine
Drug Categories
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
  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. [Article]
  2. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
  3. Cooper H, Mishriky R, Reyad AA: Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: a Meta-Analysis of Randomized Controlled Trials. Psychiatr Danub. 2020 Spring;32(1):36-45. doi: 10.24869/psyd.2020.36. [Article]
  4. Nakamura T, Kubota T, Iwakaji A, Imada M, Kapas M, Morio Y: Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment). Drug Des Devel Ther. 2016 Jan 14;10:327-38. doi: 10.2147/DDDT.S95100. eCollection 2016. [Article]
  5. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
  6. Roberts RJ, Findlay LJ, El-Mallakh PL, El-Mallakh RS: Update on schizophrenia and bipolar disorder: focus on cariprazine. Neuropsychiatr Dis Treat. 2016 Jul 25;12:1837-42. doi: 10.2147/NDT.S97616. eCollection 2016. [Article]
  7. Brisch R, Saniotis A, Wolf R, Bielau H, Bernstein HG, Steiner J, Bogerts B, Braun K, Jankowski Z, Kumaratilake J, Henneberg M, Gos T: The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry. 2014 May 19;5:47. doi: 10.3389/fpsyt.2014.00047. eCollection 2014. [Article]
  8. Ashok AH, Marques TR, Jauhar S, Nour MM, Goodwin GM, Young AH, Howes OD: The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry. 2017 May;22(5):666-679. doi: 10.1038/mp.2017.16. Epub 2017 Mar 14. [Article]
  9. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
  10. Cision PR Newswire: Health Canada Approves VRAYLAR® (cariprazine) for the Treatment of Bipolar l Disorder and Schizophrenia in Adults [Link]
  11. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules (September 2022) [Link]
KEGG Drug
D09997
PubChem Compound
11154555
PubChem Substance
310264859
ChemSpider
25999972
BindingDB
50382290
RxNav
1667655
ChEBI
90933
ChEMBL
CHEMBL2028019
ZINC
ZINC000100907004
PDBe Ligand
7RU
Drugs.com
Drugs.com Drug Page
Wikipedia
Cariprazine
PDB Entries
7vod

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingBasic ScienceDepression, Bipolar1
4Not Yet RecruitingTreatmentMajor Depressive Disorder (MDD)1
4Not Yet RecruitingTreatmentSocial Anxiety Disorder (SAD)1
4RecruitingDiagnosticTreatment Resistant Schizophrenia1
4RecruitingTreatmentAttention Deficit Hyperactivity Disorder (ADHD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral1.635 MG
CapsuleOral1.5 mg
CapsuleOral3.27 MG
CapsuleOral3 mg
CapsuleOral4.905 MG
CapsuleOral4.5 mg
CapsuleOral6.54 MG
CapsuleOral6 mg
Capsule, gelatin coatedOral1.5 mg
Capsule, gelatin coatedOral3.000 mg
Capsule, gelatin coatedOral4.500 mg
Capsule, gelatin coatedOral6.000 mg
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)Region
US7737142No2010-06-152027-03-27US flag
US7943621No2011-05-172028-12-16US flag
USRE47350No2019-04-162029-07-16US flag
USRE49110No2009-07-162029-07-16US flag
USRE49302No2009-07-162029-07-16US flag

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
Polarizability48.36 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/MSsplash10-004i-0000900000-be1b366aaa6d53c1a44d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-2008900000-bad7cca66c97d1dfb647
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0003900000-e14a946dc5ace04b96fa
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-005c-9016600000-b655eb7acd3e16e8f807
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-056u-0985200000-fc29f1675a558ecaec3b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000x-9526200000-b1e0695c7f9f2dd4b9c1
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-197.39671
predicted
DeepCCS 1.0 (2019)
[M+H]+199.75471
predicted
DeepCCS 1.0 (2019)
[M+Na]+206.23772
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. Dopamine D3 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial agonist
Curator comments
Inhibition constant (Ki) = 0.085 nmol/L
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. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
  2. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
  3. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
  4. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]
Details2. Dopamine D2 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial agonist
Curator comments
Inhibition constant (Ki) = 0.49 nmol/L for D2L, 0.69 nmol/L for D2S
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. McCormack PL: Cariprazine: First Global Approval. Drugs. 2015 Nov;75(17):2035-43. doi: 10.1007/s40265-015-0494-7. [Article]
  2. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
  3. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
  4. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]
Details3. 5-hydroxytryptamine receptor 1A
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial agonist
Curator comments
Inhibition constant (Ki) = 2.6 nmol/L
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. [Article]
  2. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
  3. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
  4. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]
Details4. 5-hydroxytryptamine receptor 2B
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibition constant (Ki) = 0.58 nmol/L
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. [Article]
  2. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
  3. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
Details5. 5-hydroxytryptamine receptor 2A
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibition constant (Ki) = 18.8 mmol/L
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. [Article]
  2. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
  3. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
Details6. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibition constant (Ki) = 23 nmol/L
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. [Article]
  2. Stahl SM: Mechanism of action of cariprazine. CNS Spectr. 2016 Apr;21(2):123-7. doi: 10.1017/S1092852916000043. Epub 2016 Mar 9. [Article]
Details7. 5-hydroxytryptamine receptor 2C
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibition constant (Ki) = 155 nM
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, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
Details8. Alpha-1A adrenergic receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibition constant (Ki) = 134 nM
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
Curator comments
Based on in vitro results, cariprazine has the potential to act as a CYP3A4/3A5 inducer at the intestinal level. Cariprazine and its major active metabolites were weak inhibitors in vitro.
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. [Article]
  2. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
  3. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]
Details2. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
Cariprazine and its major active metabolites were weak inhibitors in vitro.
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. [Article]
  2. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
  3. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]
Details3. Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
Curator comments
Based on in vitro results, cariprazine has the potential to act as a CYP3A4/3A5 inducer at the intestinal level.
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]
Details4. Cytochrome P450 1A2
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Cariprazine and its major active metabolites were weak inhibitors in vitro.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
Details5. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Cariprazine and its major active metabolites were weak inhibitors in vitro.
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
Details6. Cytochrome P450 2C19
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Cariprazine, but not its active metabolites, was a weak inhibitor in vitro.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]
Details7. Cytochrome P450 2E1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Cariprazine, but not its active metabolites, was a weak inhibitor in vitro.
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. FDA Approved Drug Products: VRAYLAR (cariprazine) capsules, for oral use [Link]

Transporters

Details1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Based on in vitro results, cariprazine has the potential to act as a weak P-glycoprotein (P-gp) inhibitor at the intestinal level.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Health Canada Approved Drug Products: VRAYLAR (Cariprazine) Oral Capsules [Link]

Drug created at November 18, 2007 18:29 / Updated at February 02, 2024 22:52