Identification

Name
Brexpiprazole
Accession Number
DB09128
Type
Small Molecule
Groups
Approved
Description

Brexpiprazole is a novel D2 dopamine and serotonin 1A partial agonist, called serotonin-dopamine activity modulator (SDAM), and a potent antagonist of serotonin 2A receptors, noradrenergic alpha 1B and 2C receptors. Brexpiprazole is approved for the treatment of schizophrenia, and as an adjunctive treatment for major depressive disorder (MDD). Although it failed Phase II clinical trials for ADHD, it has been designed to provide improved efficacy and tolerability (e.g., less akathisia, restlessness and/or insomnia) over established adjunctive treatments for major depressive disorder (MDD).

Structure
Thumb
Synonyms
Not Available
External IDs
OPC-34712
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RexultiTablet0.5 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada
RexultiTablet.25 mg/1OralOtsuka Pharmaceutical Co., Ltd.2015-07-10Not applicableUs
RexultiTablet4 mg/1OralOtsuka Pharmaceutical Co., Ltd.2015-07-10Not applicableUs
RexultiTablet1 mg/1OralOtsuka Pharmaceutical Co., Ltd.2015-07-10Not applicableUs
RexultiTablet2 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada
RexultiTablet0.25 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada
RexultiTablet3 mg/1OralOtsuka Pharmaceutical Co., Ltd.2015-07-10Not applicableUs
RexultiTablet4 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada
RexultiTablet1 mgOralOtsuka Pharmaceutical Co., Ltd.2017-04-19Not applicableCanada
RexultiTablet.5 mg/1OralOtsuka Pharmaceutical Co., Ltd.2015-07-10Not applicableUs
Categories
UNII
2J3YBM1K8C
CAS number
913611-97-9
Weight
Average: 433.57
Monoisotopic: 433.182398295
Chemical Formula
C25H27N3O2S
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

Pharmacology

Indication

As an adjunctive treatment of major depressive disorder (MDD) and for treatment of schizophrenia.

Structured Indications
Pharmacodynamics
Not Available
Mechanism of action

Although the mechanism of action of brexpiprazole in the treatment of MDD and schizophrenia is unclear, the efficacy of brexpiprazole may be attributed to partial agonist activity at serotonin 1A and dopamine D2 receptors, and antagonist activity at serotonin 2A receptors.

TargetActionsOrganism
A5-hydroxytryptamine receptor 1A
agonist
partial agonist
Human
AD(2) dopamine receptor
agonist
partial agonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
AAlpha-2C adrenergic receptor
antagonist
Human
AAlpha-1B adrenergic receptor
antagonist
Human
Absorption

Brexpiprazole reaches peak plasma concentration within 4 hours of administration, and steady state occurs within 10-12 days of dosing. Oral bioavailability is 95%, and can be administered with or without food.

Volume of distribution

Intravenous volume of distribution is 1.56L/kg.

Protein binding

>99% protein bound in plasma to serum albumin and α1-acid glycoprotein. Based on in vitro studies, protein binding is not affected by warfarin, diazepam, or digitoxin.

Metabolism

Metabolized mainly by CYP3A4 and CYP2D6 enzymes into its major metabolite, DM-3411. DM-3411 is not considered to contribute any therapeutic effect.

Route of elimination

Approximately 25% urinary and 46% fecal excretion. <1% and ~14% of the unchanged drug was recovered in the urine and feces, respectively.

Half life

Brexpiprazole and its major metabolite, DM-3411 have half lives of 91 and 96 hours respectively.

Clearance

19.8mL/h/kg

Toxicity

The most commonly observed adverse effects include: weight increase, akathisia, somnolence, tremor and nasopharyngitis. Neonates are at risk for extrapyramidal and/or withdrawal symptoms if exposed to an antipsychotic drug during the third trimester of development.

Affected organisms
Not Available
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
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamineBrexpiprazole may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamineBrexpiprazole may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.Experimental
3,4-MethylenedioxyamphetamineBrexpiprazole may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamineBrexpiprazole may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.Experimental, Illicit
AbirateroneThe serum concentration of Brexpiprazole can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe serum concentration of Brexpiprazole can be increased when it is combined with Amiodarone.Approved, Investigational
AmisulprideBrexpiprazole may increase the antipsychotic activities of Amisulpride.Approved, Investigational
AmphetamineBrexpiprazole may decrease the stimulatory activities of Amphetamine.Approved, Illicit
AprepitantThe serum concentration of Brexpiprazole can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe serum concentration of Brexpiprazole can be increased when it is combined with Artemether.Approved
AtazanavirThe serum concentration of Brexpiprazole can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe serum concentration of Brexpiprazole can be increased when it is combined with Atomoxetine.Approved
BenzphetamineBrexpiprazole may decrease the stimulatory activities of Benzphetamine.Approved, Illicit
BetaxololThe serum concentration of Brexpiprazole can be increased when it is combined with Betaxolol.Approved
BoceprevirThe serum concentration of Brexpiprazole can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe serum concentration of Brexpiprazole can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Brexpiprazole can be decreased when it is combined with Bosentan.Approved, Investigational
BupropionThe serum concentration of Brexpiprazole can be increased when it is combined with Bupropion.Approved
CarbamazepineThe serum concentration of Brexpiprazole can be decreased when it is combined with Carbamazepine.Approved, Investigational
CelecoxibThe serum concentration of Brexpiprazole can be increased when it is combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Brexpiprazole can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Brexpiprazole can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorphentermineBrexpiprazole may decrease the stimulatory activities of Chlorphentermine.Illicit, Withdrawn
ChlorpromazineThe serum concentration of Brexpiprazole can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe serum concentration of Brexpiprazole can be increased when it is combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe serum concentration of Brexpiprazole can be increased when it is combined with Cimetidine.Approved
CinacalcetThe serum concentration of Brexpiprazole can be increased when it is combined with Cinacalcet.Approved
CitalopramThe serum concentration of Brexpiprazole can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Brexpiprazole can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Brexpiprazole can be increased when it is combined with Clemastine.Approved
ClobazamThe serum concentration of Brexpiprazole can be increased when it is combined with Clobazam.Approved, Illicit
ClomipramineThe serum concentration of Brexpiprazole can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineThe serum concentration of Brexpiprazole can be increased when it is combined with Clozapine.Approved
CobicistatThe serum concentration of Brexpiprazole can be increased when it is combined with Cobicistat.Approved
CocaineThe serum concentration of Brexpiprazole can be increased when it is combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Brexpiprazole can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe serum concentration of Brexpiprazole can be increased when it is combined with Crizotinib.Approved
CyclosporineThe serum concentration of Brexpiprazole can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Brexpiprazole can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe serum concentration of Brexpiprazole can be increased when it is combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Brexpiprazole can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Brexpiprazole can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Brexpiprazole can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Brexpiprazole can be increased when it is combined with Delavirdine.Approved
DesipramineThe serum concentration of Brexpiprazole can be increased when it is combined with Desipramine.Approved
DextroamphetamineBrexpiprazole may decrease the stimulatory activities of Dextroamphetamine.Approved, Illicit
DiethylpropionBrexpiprazole may decrease the stimulatory activities of Diethylpropion.Approved, Illicit
DihydroergotamineThe serum concentration of Brexpiprazole can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Brexpiprazole can be increased when it is combined with Diltiazem.Approved
DiphenhydramineThe serum concentration of Brexpiprazole can be increased when it is combined with Diphenhydramine.Approved
DosulepinThe serum concentration of Brexpiprazole can be increased when it is combined with Dosulepin.Approved
DoxycyclineThe serum concentration of Brexpiprazole can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe serum concentration of Brexpiprazole can be increased when it is combined with Dronedarone.Approved
DuloxetineThe serum concentration of Brexpiprazole can be increased when it is combined with Duloxetine.Approved
EliglustatThe serum concentration of Brexpiprazole can be increased when it is combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Brexpiprazole can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe serum concentration of Brexpiprazole can be increased when it is combined with Erythromycin.Approved, Vet Approved
FluconazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Brexpiprazole can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe serum concentration of Brexpiprazole can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Brexpiprazole can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Brexpiprazole can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Brexpiprazole can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Brexpiprazole can be increased when it is combined with Fusidic Acid.Approved
GepefrineBrexpiprazole may decrease the stimulatory activities of Gepefrine.Experimental
HaloperidolThe serum concentration of Brexpiprazole can be increased when it is combined with Haloperidol.Approved
HydroxyamphetamineBrexpiprazole may decrease the stimulatory activities of Hydroxyamphetamine.Approved
IdelalisibThe serum concentration of Brexpiprazole can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Brexpiprazole can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Brexpiprazole can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Brexpiprazole can be increased when it is combined with Indinavir.Approved
Iofetamine I-123Brexpiprazole may decrease the stimulatory activities of Iofetamine I-123.Approved
IsavuconazoniumThe serum concentration of Brexpiprazole can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsoniazidThe serum concentration of Brexpiprazole can be increased when it is combined with Isoniazid.Approved
IsradipineThe serum concentration of Brexpiprazole can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Brexpiprazole can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Ketoconazole.Approved, Investigational
LisdexamfetamineBrexpiprazole may decrease the stimulatory activities of Lisdexamfetamine.Approved, Investigational
LithiumLithium may increase the neurotoxic activities of Brexpiprazole.Approved
LopinavirThe serum concentration of Brexpiprazole can be increased when it is combined with Lopinavir.Approved
LorcaserinThe serum concentration of Brexpiprazole can be increased when it is combined with Lorcaserin.Approved
LovastatinThe serum concentration of Brexpiprazole can be increased when it is combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Brexpiprazole can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe serum concentration of Brexpiprazole can be increased when it is combined with Lumefantrine.Approved
ManidipineThe serum concentration of Brexpiprazole can be increased when it is combined with Manidipine.Approved, Investigational
MephedroneBrexpiprazole may decrease the stimulatory activities of Mephedrone.Investigational
MephentermineBrexpiprazole may decrease the stimulatory activities of Mephentermine.Approved
MequitazineBrexpiprazole may increase the arrhythmogenic activities of Mequitazine.Approved
MethadoneThe serum concentration of Brexpiprazole can be increased when it is combined with Methadone.Approved
MethamphetamineBrexpiprazole may decrease the stimulatory activities of Methamphetamine.Approved, Illicit
MethotrimeprazineThe serum concentration of Brexpiprazole can be increased when it is combined with Methotrimeprazine.Approved
MethoxyphenamineBrexpiprazole may decrease the stimulatory activities of Methoxyphenamine.Experimental
MethylphenidateThe risk or severity of adverse effects can be increased when Brexpiprazole is combined with Methylphenidate.Approved, Investigational
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Brexpiprazole.Approved, Investigational
MetoprololThe serum concentration of Brexpiprazole can be increased when it is combined with Metoprolol.Approved, Investigational
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Brexpiprazole.Approved
MidomafetamineBrexpiprazole may decrease the stimulatory activities of Midomafetamine.Experimental, Illicit, Investigational
MidostaurinThe serum concentration of Brexpiprazole can be increased when it is combined with Midostaurin.Approved
MifepristoneThe serum concentration of Brexpiprazole can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe serum concentration of Brexpiprazole can be increased when it is combined with Mirabegron.Approved
MitotaneThe serum concentration of Brexpiprazole can be decreased when it is combined with Mitotane.Approved
MMDABrexpiprazole may decrease the stimulatory activities of MMDA.Experimental, Illicit
NefazodoneThe serum concentration of Brexpiprazole can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Brexpiprazole can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Brexpiprazole can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Brexpiprazole can be decreased when it is combined with Nevirapine.Approved
NicardipineThe serum concentration of Brexpiprazole can be increased when it is combined with Nicardipine.Approved
NilotinibThe serum concentration of Brexpiprazole can be increased when it is combined with Nilotinib.Approved, Investigational
OlaparibThe serum concentration of Brexpiprazole can be increased when it is combined with Olaparib.Approved
OsimertinibThe serum concentration of Brexpiprazole can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Brexpiprazole can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Brexpiprazole can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe serum concentration of Brexpiprazole can be increased when it is combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Brexpiprazole can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe serum concentration of Brexpiprazole can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe serum concentration of Brexpiprazole can be decreased when it is combined with Phenobarbital.Approved
PhentermineBrexpiprazole may decrease the stimulatory activities of Phentermine.Approved, Illicit
PhenytoinThe serum concentration of Brexpiprazole can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Brexpiprazole can be decreased when it is combined with Primidone.Approved, Vet Approved
PromazineThe serum concentration of Brexpiprazole can be increased when it is combined with Promazine.Approved, Vet Approved
PseudoephedrineBrexpiprazole may decrease the stimulatory activities of Pseudoephedrine.Approved
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Brexpiprazole.Approved
QuinidineThe serum concentration of Brexpiprazole can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Brexpiprazole can be increased when it is combined with Quinine.Approved
RanolazineThe serum concentration of Brexpiprazole can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Brexpiprazole can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Brexpiprazole can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Brexpiprazole can be decreased when it is combined with Rifapentine.Approved
RitobegronBrexpiprazole may decrease the stimulatory activities of Ritobegron.Investigational
RitonavirThe serum concentration of Brexpiprazole can be increased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Brexpiprazole can be increased when it is combined with Rolapitant.Approved
RopiniroleThe serum concentration of Brexpiprazole can be increased when it is combined with Ropinirole.Approved, Investigational
RucaparibThe serum concentration of Brexpiprazole can be increased when it is combined with Rucaparib.Approved, Investigational
SaquinavirThe serum concentration of Brexpiprazole can be increased when it is combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Brexpiprazole can be decreased when used in combination with Sarilumab.Approved
SertralineThe serum concentration of Brexpiprazole can be increased when it is combined with Sertraline.Approved
SildenafilThe serum concentration of Brexpiprazole can be increased when it is combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Brexpiprazole can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Brexpiprazole can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Brexpiprazole can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Brexpiprazole can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
SulpirideBrexpiprazole may increase the antipsychotic activities of Sulpiride.Approved, Investigational
TelaprevirThe serum concentration of Brexpiprazole can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Brexpiprazole can be increased when it is combined with Telithromycin.Approved
TerbinafineThe serum concentration of Brexpiprazole can be increased when it is combined with Terbinafine.Approved, Investigational, Vet Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Brexpiprazole.Approved
ThioridazineThe serum concentration of Brexpiprazole can be increased when it is combined with Thioridazine.Approved, Withdrawn
TiclopidineThe serum concentration of Brexpiprazole can be increased when it is combined with Ticlopidine.Approved
TipranavirThe serum concentration of Brexpiprazole can be increased when it is combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Brexpiprazole can be decreased when it is combined with Tocilizumab.Approved
TranylcypromineThe serum concentration of Brexpiprazole can be increased when it is combined with Tranylcypromine.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Brexpiprazole.Approved, Investigational
VemurafenibThe serum concentration of Brexpiprazole can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe serum concentration of Brexpiprazole can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Brexpiprazole can be increased when it is combined with Verapamil.Approved
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Brexpiprazole.Approved
VoriconazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Voriconazole.Approved, Investigational
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Brexpiprazole.Approved
ZiprasidoneThe serum concentration of Brexpiprazole can be increased when it is combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [PubMed:26310190]
  2. Citrome L, Stensbol TB, Maeda K: The preclinical profile of brexpiprazole: what is its clinical relevance for the treatment of psychiatric disorders? Expert Rev Neurother. 2015 Oct;15(10):1219-29. doi: 10.1586/14737175.2015.1086269. Epub 2015 Sep 24. [PubMed:26402059]
  3. Citrome L: Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2015 Sep;69(9):978-97. doi: 10.1111/ijcp.12714. Epub 2015 Aug 6. [PubMed:26250067]
External Links
KEGG Drug
D10309
PubChem Compound
11978813
PubChem Substance
310265043
ChemSpider
10152155
BindingDB
194780
ChEBI
134716
ChEMBL
CHEMBL2105760
PharmGKB
PA166160053
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Brexpiprazole
ATC Codes
N05AX16 — Brexpiprazole
AHFS Codes
  • 28:16.08.04 — Atypical Antipsychotics
FDA label
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceSchizophrenic Disorders1
1CompletedTreatmentHealthy Adult Males1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentPsychiatric Disorders / Schizophrenic Disorders1
1CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
1CompletedTreatmentSchizophrenic Disorders3
1RecruitingTreatmentAdhd / Autism, Early Infantile / Bipolar I Disorder / Oppositional Defiant Disorder1
1TerminatedHealth Services ResearchSchizophrenic Disorders1
2CompletedTreatmentAttention Deficit Hyperactivity Disorder (ADHD)1
2CompletedTreatmentMajor Depressive Disorder (MDD)3
2CompletedTreatmentSchizophrenic Disorders2
2RecruitingTreatmentPost Traumatic Stress Disorder (PTSD)1
2RecruitingTreatmentStress Disorders, Post-Traumatic1
2, 3CompletedTreatmentSchizophrenic Disorders1
3CompletedTreatmentAcute Schizophrenia3
3CompletedTreatmentAgitation Associated With / Alzheimer's Disease (AD) / Alzheimer's Type / Nervous System Diseases / Psychiatric Disorder NOS2
3CompletedTreatmentDepression / Depressive Disorders / Major Depressive Disorder (MDD) / Moods Disorders / Psychiatric Disorder NOS5
3CompletedTreatmentFeeling Anxious / Major Depressive Disorder (MDD)1
3CompletedTreatmentIrritability / Major Depressive Disorder (MDD)1
3CompletedTreatmentMajor Depressive Disorder (MDD)3
3CompletedTreatmentSchizophrenia With Impulsivity1
3CompletedTreatmentSchizophrenic Disorders6
3CompletedTreatmentSleep Disturbances1
3Not Yet RecruitingTreatmentAcute Mania / Bipolar I Disorder1
3RecruitingSupportive CareSchizophrenic Disorders1
3RecruitingTreatmentAcute Manic episode / Bipolar I Disorder2
3RecruitingTreatmentSchizophrenic Disorders1
3TerminatedTreatmentMajor Depressive Disorder (MDD)2
3TerminatedTreatmentPost-Traumatic Stress Disorder (PTSD) / PTSD1
3WithdrawnTreatmentMajor Depressive Disorder and Irritability1
3WithdrawnTreatmentSchizophrenic Disorders1
4RecruitingTreatmentDepression1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral.25 mg/1
TabletOral.5 mg/1
TabletOral0.25 mg
TabletOral0.5 mg
TabletOral1 mg
TabletOral1 mg/1
TabletOral2 mg
TabletOral2 mg/1
TabletOral3 mg
TabletOral3 mg/1
TabletOral4 mg
TabletOral4 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8349840No2006-04-122026-04-12Us
US8618109No2006-04-122026-04-12Us
US7888362No2007-02-232027-02-23Us

Properties

State
Solid
Experimental Properties
Not Available
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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
N-arylpiperazine / Dihydroquinolone / Dihydroquinoline / Quinoline / Benzothiophene / 1-benzothiophene / Dialkylarylamine / Tertiary aliphatic/aromatic amine / Alkyl aryl ether / Pyridinone
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. [PubMed:24947465]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. [PubMed:24947465]
Kind
Protein
Organism
Human
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
  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. [PubMed:24947465]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. [PubMed:25225185]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. [PubMed:25225185]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:26310190]
Kind
Protein
Organism
Human
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. [PubMed:26310190]

Drug created on September 28, 2015 17:01 / Updated on January 15, 2018 08:58