Brexpiprazole

Identification

Summary

Brexpiprazole is a serotonin–dopamine activity modulator used in the treatment of major depressive disorder as an adjunct, schizophrenia, and agitation associated with dementia due to Alzheimer’s disease.

Brand Names
Rexulti
Generic Name
Brexpiprazole
DrugBank Accession Number
DB09128
Background

Brexpiprazole is an atypical antipsychotic and a novel D2 dopamine and serotonin 1A partial agonist called serotonin-dopamine activity modulator (SDAM). It has a high affinity for serotonin, dopamine and alpha (α)-adrenergic receptors.8 Although it is structurally similar to aripiprazole, brexpiprazole has different binding affinities for dopamine and serotonin receptors. Compared to aripiprazole, brexpiprazole has less potential for partial agonist-mediated adverse effects such as extrapyramidal symptoms, which is attributed to lower intrinsic activity at the D2 receptor. It also displays stronger antagonism at the 5-HT1A and 5-HT2A receptors.2,5,6

Brexpiprazole was first approved by the FDA on July 10, 2015.2 Currently approved for the treatment of depression, schizophrenia, and agitation associated with dementia due to Alzheimer’s disease, brexpiprazole has also been investigated in other psychiatric disorders, such as post-traumatic stress disorder.1

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 433.57
Monoisotopic: 433.182398295
Chemical Formula
C25H27N3O2S
Synonyms
  • Brexpiprazole
  • Lu-AF41156
External IDs
  • OPC 34712
  • OPC-34712
  • OPC34712

Pharmacology

Indication

Brexpiprazole is indicated as adjunctive therapy to antidepressants for the treatment of major depressive disorder in adults.7 It is also indicated for the treatment of schizophrenia in patients 13 years of age and older.7

Brexpiprazole is also indicated for the treatment of agitation associated with dementia due to Alzheimer’s disease; however, it is not indicated as an as-needed (“prn”) treatment for this condition.8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAgitation••••••••••••••••••
Adjunct therapy in treatment ofMajor depressive disorder (mdd)•••••••••••••••••••••••
Treatment ofSchizophrenia•••••••••••••••••• •••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Brexpiprazole is an atypical antipsychotic agent used to ameliorate the symptoms of psychiatric conditions, such as cognitive deficits and affective symptoms.2 Brexpiprazole has affinity (expressed as Ki) for multiple monoaminergic receptors including serotonin 5-HT1A (0.12 nM), 5-HT2A (0.47 nM), 5-HT2B (1.9 nM), 5-HT7 (3.7 nM), dopamine D2 (0.30 nM), D3 (1.1 nM), and noradrenergic α1A (3.8 nM), α1B (0.17 nM), α1D (2.6 nM), and α2C (0.59 nM) receptors. Brexpiprazole acts as a partial agonist at the 5-HT1A, D2, and D3 receptors and as an antagonist at 5-HT2A, 5-HT2B, 5-HT7, α1A, α1B, α1D, and α2C receptors. Brexpiprazole also exhibits affinity for histamine H1 receptor (19 nM) and for muscarinic M1 receptor (67% inhibition at 10 µM).8

Mechanism of action

Although the exact mechanism of action of brexpiprazole in psychiatric disorders has not been fully elucidated, the efficacy of brexpiprazole may be attributed to combined partial agonist activity at 5-HT1A and dopamine D2 receptors, and antagonist activity at 5-HT2A receptors. Brexpiprazole binds to these receptors with subnanomolar affinities.1,3,8 These therapeutic targets have been implicated in psychiatric conditions such as schizophrenia and depression. Partial D2 receptor agonism allows the drug to stimulate D2 receptors under low dopamine conditions, while attenuating their activation when dopamine levels are high. Partial agonism at 5-HT1A receptors may be tied to improved memory function and cognitive performance. Antagonism at α-adrenergic receptors has also been implicated in schizophrenia and depression.2,4

TargetActionsOrganism
U5-hydroxytryptamine receptor 1A
partial agonist
Humans
UDopamine D2 receptor
partial agonist
Humans
UDopamine D3 receptor
partial agonist
Humans
U5-hydroxytryptamine receptor 2A
antagonist
Humans
U5-hydroxytryptamine receptor 2B
antagonist
Humans
U5-hydroxytryptamine receptor 7
antagonist
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
UAlpha-1D adrenergic receptor
antagonist
Humans
UAlpha-2C adrenergic receptor
antagonist
Humans
UHistamine H1 receptor
antagonist
Humans
UMuscarinic acetylcholine receptor M1
antagonist
Humans
Absorption

After a single-dose administration, the Tmax was four hours and the absolute oral bioavailability was 95%. Brexpiprazole steady-state concentrations were attained within 10 to 12 days of dosing. After single and multiple once-daily dose administration, the Cmax and AUC increased dose-proportionally.8

A high-fat meal did not significantly affect the Cmax or AUC of brexpiprazole.8

Volume of distribution

The volume of distribution of brexpiprazole following intravenous administration is 1.56 ± 0.42 L/kg, indicating extravascular distribution.8

Protein binding

In vitro, brexpiprazole was 99% bound to plasma proteins, mainly serum albumin and α1-acid glycoprotein.8

Metabolism

According to in vitro studies, brexpiprazole is mainly metabolized by CYP3A4 and CYP2D6. Brexpiprazole and its major metabolite, DM-3411, were the predominant drug moieties in the systemic circulation following single and multiple dose administration. At steady-state, DM-3411 represented 23% to 48% of brexpiprazole exposure (AUC) in plasma. DM-3411 is considered not to be pharmacologically active.8

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Route of elimination

Following a single oral dose of radiolabeled brexpiprazole, approximately 25% and 46% of radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged brexpiprazole was excreted in the urine, and approximately 14% of the oral dose was recovered unchanged in the feces.8

Half-life

After multiple once-daily administrations, the terminal elimination half-lives of brexpiprazole and its major metabolite, DM-3411, were 91 hours and 86 hours, respectively.8

Clearance

Apparent oral clearance of brexpiprazole after once-daily administration is 19.8 (±11.4) mL/h/kg.8

Adverse Effects
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Toxicity

There is limited information regarding acute toxicity and human overdosage with brexpiprazole. Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers. Oral activated charcoal and sorbitol (50 g/240 mL), administered one hour after ingesting oral brexpiprazole, decreased brexpiprazole Cmax and area under the curve (AUC) by approximately 5% to 23% and 31% to 39% respectively; however, there is insufficient information available on the therapeutic potential of activated charcoal in treating an overdose with brexpiprazole. There is no information on the effect of hemodialysis in treating an overdose with brexpiprazole; hemodialysis is unlikely to be useful because brexpiprazole is highly bound to plasma proteins.8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirement.Details

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.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Brexpiprazole is combined with 1,2-Benzodiazepine.
AbametapirThe serum concentration of Brexpiprazole can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Brexpiprazole can be increased when combined with Abatacept.
AbirateroneThe metabolism of Brexpiprazole can be decreased when combined with Abiraterone.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Brexpiprazole.
Food Interactions
  • Avoid St. John's Wort. This herb induces the CYP3A metabolism of brexpiprazole and may reduce its serum concentration. The dose of Brexpiprazole should be doubled if administered with St. John's wort.
  • Drink plenty of fluids.
  • Take with or without food. Food does not significantly affect brexpiprazole exposure.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Brexpiprazole dihydrochlorideNot Available913612-38-1Not applicable
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RexultiTablet2 mg/1OralREMEDYREPACK INC.2022-10-03Not applicableUS flag
RexultiTablet2 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada flag
RexultiTablet0.25 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada flag
RexultiTablet3 mg/1OralOtsuka America Pharmaceutical, Inc.2015-07-10Not applicableUS flag
RexultiTablet0.5 mg/1OralOtsuka America Pharmaceutical, Inc.2015-07-10Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BrexpiprazoleTablet, film coated0.5 mg/1OralCamber Pharmaceuticals, Inc.2023-11-20Not applicableUS flag
BrexpiprazoleTablet3 mg/1OralAjanta Pharma USA Inc.2023-02-03Not applicableUS flag
BrexpiprazoleTablet0.5 mg/1OralAjanta Pharma USA Inc.2023-02-03Not applicableUS flag
BrexpiprazoleTablet, film coated3 mg/1OralAmneal Pharmaceuticals NY LLC2023-02-07Not applicableUS flag
BrexpiprazoleTablet, film coated0.5 mg/1OralAmneal Pharmaceuticals NY LLC2023-02-07Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
RexultiBrexpiprazole (1 mg/1) + Brexpiprazole (2 mg/1)Kit; TabletOralOtsuka America Pharmaceutical, Inc.2015-07-10Not applicableUS flag
RexultiBrexpiprazole (0.5 mg/1) + Brexpiprazole (1 mg/1)Kit; TabletOralOtsuka America Pharmaceutical, Inc.2015-07-10Not applicableUS flag
RexultiBrexpiprazole (0.5 mg) + Brexpiprazole (1 mg)Kit; TabletOralOtsuka Pharmaceutical Co., Ltd.2019-06-082022-10-31Canada flag
RexultiBrexpiprazole (1 mg/1) + Brexpiprazole (2 mg/1)Kit; TabletOralOtsuka America Pharmaceutical, Inc.2015-07-10Not applicableUS flag
RexultiBrexpiprazole (1 mg) + Brexpiprazole (2 mg)Kit; TabletOralOtsuka Pharmaceutical Co., Ltd.Not applicableNot applicableCanada flag

Categories

ATC Codes
N05AX16 — Brexpiprazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
N-arylpiperazines
Alternative Parents
Hydroquinolones / Hydroquinolines / 1-benzothiophenes / Dialkylarylamines / N-alkylpiperazines / Pyridinones / Alkyl aryl ethers / Benzenoids / Thiophenes / Heteroaromatic compounds
show 6 more
Substituents
1-benzothiophene / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzothiophene / Dialkylarylamine / Dihydroquinoline / Dihydroquinolone
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
2J3YBM1K8C
CAS number
913611-97-9
InChI Key
ZKIAIYBUSXZPLP-UHFFFAOYSA-N
InChI
InChI=1S/C25H27N3O2S/c29-25-9-7-19-6-8-20(18-22(19)26-25)30-16-2-1-11-27-12-14-28(15-13-27)23-4-3-5-24-21(23)10-17-31-24/h3-10,17-18H,1-2,11-16H2,(H,26,29)
IUPAC Name
7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}-1,2-dihydroquinolin-2-one
SMILES
O=C1NC2=CC(OCCCCN3CCN(CC3)C3=C4C=CSC4=CC=C3)=CC=C2C=C1

References

General References
  1. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  2. Das S, Barnwal P, Winston A B, Mondal S, Saha I: Brexpiprazole: so far so good. Ther Adv Psychopharmacol. 2016 Feb;6(1):39-54. doi: 10.1177/2045125315614739. [Article]
  3. Diefenderfer LA, Iuppa C: Brexpiprazole: A review of a new treatment option for schizophrenia and major depressive disorder. Ment Health Clin. 2018 Mar 23;7(5):207-212. doi: 10.9740/mhc.2017.09.207. eCollection 2017 Sep. [Article]
  4. Brasso C, Colli G, Sgro R, Bellino S, Bozzatello P, Montemagni C, Villari V, Rocca P: Efficacy of Serotonin and Dopamine Activity Modulators in the Treatment of Negative Symptoms in Schizophrenia: A Rapid Review. Biomedicines. 2023 Mar 16;11(3):921. doi: 10.3390/biomedicines11030921. [Article]
  5. Eaves S, Rey JA: Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. P T. 2016 Jul;41(7):418-22. [Article]
  6. Stahl SM: Mechanism of action of brexpiprazole: comparison with aripiprazole. CNS Spectr. 2016 Feb;21(1):1-6. doi: 10.1017/S1092852915000954. [Article]
  7. FDA Approved Drug Products: Rexulti (brexpiprazole) tablets for oral use [Link]
  8. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Human Metabolome Database
HMDB0249379
KEGG Drug
D10309
PubChem Compound
11978813
PubChem Substance
310265043
ChemSpider
10152155
BindingDB
194780
RxNav
1658314
ChEBI
134716
ChEMBL
CHEMBL2105760
ZINC
ZINC000084758479
PharmGKB
PA166160053
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Brexpiprazole

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDepression1
4CompletedTreatmentDepression, Bipolar1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4RecruitingTreatmentMajor Depressive Disorder (MDD)1
4RecruitingTreatmentSchizoaffective Disorders / Schizophrenia / Substance Use Disorders (SUD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral0.25 mg/1
Tablet, film coatedOral0.5 mg/1
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral2 mg/1
Tablet, film coatedOral3 mg/1
Tablet, film coatedOral4 mg/1
Kit; tabletOral
TabletOral0.25 mg
TabletOral0.25 mg/1
TabletOral0.5 mg/1
TabletOral0.5 mg
TabletOral1 mg/1
TabletOral1 mg
TabletOral2 mg/1
TabletOral2 mg
TabletOral3 mg/1
TabletOral3 mg
TabletOral3.000 mg
TabletOral4 mg
TabletOral4 mg/1
Tablet, film coatedOral0.25 MG
Tablet, film coatedOral0.5 MG
Tablet, film coatedOral1 MG
Tablet, film coatedOral2 MG
Tablet, film coatedOral3 MG
Tablet, film coatedOral4 MG
Tablet, coatedOral0.25 mg
Tablet, coatedOral0.5 mg
Tablet, coatedOral1 mg
Tablet, coatedOral2 mg
Tablet, coatedOral3 mg
Tablet, coatedOral4 mg
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8349840No2013-01-082026-04-12US flag
US8618109No2013-12-312026-04-12US flag
US7888362No2011-02-152027-02-23US flag
US9839637No2017-12-122026-04-12US flag
US10307419No2019-06-042032-10-12US flag
USRE48059No2020-06-232026-04-12US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)135.1https://www.axonmedchem.com/media/certificates/2335-MSDS-B1.pdf
boiling point (°C)675.2https://file.medchemexpress.com/batch_PDF/HY-15780/Brexpiprazole-SDS-MedChemExpress.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.00227 mg/mLALOGPS
logP5.38ALOGPS
logP4.65Chemaxon
logS-5.3ALOGPS
pKa (Strongest Acidic)13.56Chemaxon
pKa (Strongest Basic)8.4Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area44.81 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity129.16 m3·mol-1Chemaxon
Polarizability49.48 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
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/MSsplash10-001i-0000900000-79360a4353963578bbaa
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-01q9-0010900000-c262b03c72a22d5dc909
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0014900000-4ee3c236f583e52cbb13
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0130900000-8abb263805b821d3cb70
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0890100000-f0f560068aff403e9f7b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0940200000-1b5c0ac8dd9764ea535f
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]-212.5771826
predicted
DarkChem Lite v0.1.0
[M-H]-202.61684
predicted
DeepCCS 1.0 (2019)
[M+H]+211.2298826
predicted
DarkChem Lite v0.1.0
[M+H]+205.08675
predicted
DeepCCS 1.0 (2019)
[M+Na]+211.8645826
predicted
DarkChem Lite v0.1.0
[M+Na]+212.25865
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial 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
  1. Maeda K, Sugino H, Akazawa H, Amada N, Shimada J, Futamura T, Yamashita H, Ito N, McQuade RD, Mork A, Pehrson AL, Hentzer M, Nielsen V, Bundgaard C, Arnt J, Stensbol TB, Kikuchi T: Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014 Sep;350(3):589-604. doi: 10.1124/jpet.114.213793. Epub 2014 Jun 19. [Article]
  2. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  3. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial 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
  1. Maeda K, Sugino H, Akazawa H, Amada N, Shimada J, Futamura T, Yamashita H, Ito N, McQuade RD, Mork A, Pehrson AL, Hentzer M, Nielsen V, Bundgaard C, Arnt J, Stensbol TB, Kikuchi T: Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014 Sep;350(3):589-604. doi: 10.1124/jpet.114.213793. Epub 2014 Jun 19. [Article]
  2. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  3. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial 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
  1. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Maeda K, Sugino H, Akazawa H, Amada N, Shimada J, Futamura T, Yamashita H, Ito N, McQuade RD, Mork A, Pehrson AL, Hentzer M, Nielsen V, Bundgaard C, Arnt J, Stensbol TB, Kikuchi T: Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014 Sep;350(3):589-604. doi: 10.1124/jpet.114.213793. Epub 2014 Jun 19. [Article]
  2. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  3. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  2. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  2. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
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. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  2. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
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
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Oosterhof CA, El Mansari M, Blier P: Acute effects of brexpiprazole on serotonin, dopamine, and norepinephrine systems: an in vivo electrophysiologic characterization. J Pharmacol Exp Ther. 2014 Dec;351(3):585-95. doi: 10.1124/jpet.114.218578. Epub 2014 Sep 15. [Article]
  2. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  3. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Oosterhof CA, El Mansari M, Blier P: Acute effects of brexpiprazole on serotonin, dopamine, and norepinephrine systems: an in vivo electrophysiologic characterization. J Pharmacol Exp Ther. 2014 Dec;351(3):585-95. doi: 10.1124/jpet.114.218578. Epub 2014 Sep 15. [Article]
  2. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  3. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Brexpiprazole is reported to have moderate affinity for histamine H1 receptors.
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. Das S, Barnwal P, Winston A B, Mondal S, Saha I: Brexpiprazole: so far so good. Ther Adv Psychopharmacol. 2016 Feb;6(1):39-54. doi: 10.1177/2045125315614739. [Article]
  2. Diefenderfer LA, Iuppa C: Brexpiprazole: A review of a new treatment option for schizophrenia and major depressive disorder. Ment Health Clin. 2018 Mar 23;7(5):207-212. doi: 10.9740/mhc.2017.09.207. eCollection 2017 Sep. [Article]
  3. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  4. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Brexpiprazole is reported to have very low affinity for muscarinic M1 receptors.
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Das S, Barnwal P, Winston A B, Mondal S, Saha I: Brexpiprazole: so far so good. Ther Adv Psychopharmacol. 2016 Feb;6(1):39-54. doi: 10.1177/2045125315614739. [Article]
  2. Diefenderfer LA, Iuppa C: Brexpiprazole: A review of a new treatment option for schizophrenia and major depressive disorder. Ment Health Clin. 2018 Mar 23;7(5):207-212. doi: 10.9740/mhc.2017.09.207. eCollection 2017 Sep. [Article]
  3. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  4. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
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
  1. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  2. FDA Approved Drug Products: Rexulti (brexpiprazole) tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
  1. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
  2. FDA Approved Drug Products: Rexulti (brexpiprazole) tablets for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
DM-3411, a metabolite of brexpiprazole, showed weak inhibitory effects on MATE-2K (0.156 μmol/L) in vitro. However, it is unlikely to cause clinically relevant drug interactions.
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Sasabe H, Koga T, Furukawa M, Matsunaga M, Sasahara K, Hashizume K, Oozone Y, Amunom I, Torii M, Umehara K, Kashiyama E, Takeuchi K: In vitro evaluations for pharmacokinetic drug-drug interactions of a novel serotonin-dopamine activity modulator, brexpiprazole. Xenobiotica. 2021 May;51(5):522-535. doi: 10.1080/00498254.2021.1897898. Epub 2021 Mar 11. [Article]

Drug created at September 28, 2015 23:01 / Updated at September 28, 2023 05:47