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
Structure for Brexpiprazole (DB09128)
- 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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- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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
Target Actions Organism U5-hydroxytryptamine receptor 1A partial agonistHumans UDopamine D2 receptor partial agonistHumans UDopamine D3 receptor partial agonistHumans U5-hydroxytryptamine receptor 2A antagonistHumans U5-hydroxytryptamine receptor 2B antagonistHumans U5-hydroxytryptamine receptor 7 antagonistHumans UAlpha-1A adrenergic receptor antagonistHumans UAlpha-1B adrenergic receptor antagonistHumans UAlpha-1D adrenergic receptor antagonistHumans UAlpha-2C adrenergic receptor antagonistHumans UHistamine H1 receptor antagonistHumans UMuscarinic acetylcholine receptor M1 antagonistHumans - 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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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/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2D6 CYP2D6*3 Not Available C allele Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*4 Not Available C allele Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirement. Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Brexpiprazole is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Brexpiprazole can be increased when it is combined with Abametapir. Abatacept The metabolism of Brexpiprazole can be increased when combined with Abatacept. Abiraterone The metabolism of Brexpiprazole can be decreased when combined with Abiraterone. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Brexpiprazole. Acebutolol Acebutolol may increase the orthostatic hypotensive activities of Brexpiprazole. Aceclofenac The risk or severity of hypertension can be increased when Aceclofenac is combined with Brexpiprazole. Acemetacin The risk or severity of hypertension can be increased when Brexpiprazole is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Brexpiprazole is combined with Acenocoumarol. Acetaminophen The metabolism of Brexpiprazole can be decreased when combined with Acetaminophen. 
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- 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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Ingredient UNII CAS InChI Key Brexpiprazole dihydrochloride Not Available 913612-38-1 Not applicable - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rexulti Tablet 2 mg Oral Otsuka Pharmaceutical Co., Ltd. 2017-04-19 Not applicable Canada 
Rexulti Tablet 0.25 mg Oral Otsuka Pharmaceutical Co., Ltd. 2017-04-19 Not applicable Canada Rexulti Tablet 0.5 mg/1 Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US 
Rexulti Tablet 3 mg/1 Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US Rexulti Tablet 4 mg Oral Otsuka Pharmaceutical Co., Ltd. 2017-04-19 Not applicable Canada Rexulti Tablet 1 mg Oral Otsuka Pharmaceutical Co., Ltd. 2017-04-19 Not applicable Canada Rexulti Tablet 1 mg/1 Oral Avera McKennan Hospital 2016-06-17 2017-05-24 US Rexulti Tablet 3 mg Oral Otsuka Pharmaceutical Co., Ltd. 2017-04-19 Not applicable Canada Rexulti Tablet 0.25 mg/1 Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US Rexulti Tablet 2 mg/1 Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Brexpiprazole Tablet 3 mg/1 Oral Ajanta Pharma USA Inc. 2023-02-03 Not applicable US Brexpiprazole Tablet 0.5 mg/1 Oral Ajanta Pharma USA Inc. 2023-02-03 Not applicable US Brexpiprazole Tablet, film coated 0.5 mg/1 Oral Amneal Pharmaceuticals NY LLC 2023-02-07 Not applicable US Brexpiprazole Tablet, film coated 3 mg/1 Oral Amneal Pharmaceuticals NY LLC 2023-02-07 Not applicable US Brexpiprazole Tablet 2 mg/1 Oral Ajanta Pharma USA Inc. 2023-02-03 Not applicable US Brexpiprazole Tablet 0.25 mg/1 Oral Ajanta Pharma USA Inc. 2023-02-03 Not applicable US Brexpiprazole Tablet 4 mg/1 Oral Ajanta Pharma USA Inc. 2023-02-03 Not applicable US Brexpiprazole Tablet, film coated 0.25 mg/1 Oral Amneal Pharmaceuticals NY LLC 2023-02-07 Not applicable US Brexpiprazole Tablet, film coated 2 mg/1 Oral Amneal Pharmaceuticals NY LLC 2023-02-07 Not applicable US Brexpiprazole Tablet 1 mg/1 Oral Ajanta Pharma USA Inc. 2023-02-03 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Rexulti Brexpiprazole (1 mg/1) + Brexpiprazole (2 mg/1) Kit; Tablet Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US Rexulti Brexpiprazole (0.5 mg) + Brexpiprazole (1 mg) Kit; Tablet Oral Otsuka Pharmaceutical Co., Ltd. 2019-06-08 2022-10-31 Canada Rexulti Brexpiprazole (0.5 mg/1) + Brexpiprazole (1 mg/1) Kit; Tablet Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US Rexulti Brexpiprazole (1 mg/1) + Brexpiprazole (2 mg/1) Kit; Tablet Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US Rexulti Brexpiprazole (0.5 mg) + Brexpiprazole (1 mg) Kit; Tablet Oral Otsuka Pharmaceutical Co., Ltd. 2019-06-08 2022-10-31 Canada Rexulti Brexpiprazole (1 mg) + Brexpiprazole (2 mg) Kit; Tablet Oral Otsuka Pharmaceutical Co., Ltd. Not applicable Not applicable Canada Rexulti Brexpiprazole (0.5 mg/1) + Brexpiprazole (1 mg/1) Kit; Tablet Oral Otsuka America Pharmaceutical, Inc. 2015-07-10 Not applicable US Rexulti Brexpiprazole (1 mg) + Brexpiprazole (2 mg) Kit; Tablet Oral Otsuka Pharmaceutical Co., Ltd. Not applicable Not applicable Canada
Categories
- ATC Codes
- N05AX16 — Brexpiprazole
- Drug Categories
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Antidepressive Agents
- Antidepressive Agents Indicated for Depression
- Antipsychotic Agents
- Antipsychotic Agents (Second Generation [Atypical])
- Central Nervous System Depressants
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Dopamine Agents
- Dopamine Agonists
- Dopamine D2 Receptor Agonists
- Heterocyclic Compounds, Fused-Ring
- Hyperglycemia-Associated Agents
- MATE 2 Inhibitors
- MATE inhibitors
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- Psycholeptics
- Quinolines
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Agonists
- Serotonin Receptor Antagonists
- Sulfur Compounds
- 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
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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]
- 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]
- 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]
- 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]
- Stahl SM: Mechanism of action of brexpiprazole: comparison with aripiprazole. CNS Spectr. 2016 Feb;21(1):1-6. doi: 10.1017/S1092852915000954. [Article]
- FDA Approved Drug Products: Rexulti (brexpiprazole) tablets for oral use [Link]
- FDA Approved Drug Products: REXULTI (brexpiprazole) tablets for oral use (May 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0249379
- KEGG Drug
- D10309
- PubChem Compound
- 11978813
- PubChem Substance
- 310265043
- ChemSpider
- 10152155
- BindingDB
- 194780
- 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
Phase Status Purpose Conditions Count 4 Completed Treatment Depression 1 4 Completed Treatment Depression, Bipolar 1 4 Completed Treatment Major Depressive Disorder (MDD) 1 4 Recruiting Treatment Major Depressive Disorder (MDD) 1 4 Recruiting Treatment Schizoaffective Disorders / Schizophrenia / Substance Use Disorders (SUD) 1 4 Withdrawn Basic Science Major Depressive Disorder (MDD) 1 3 Active Not Recruiting Supportive Care Schizophrenia 1 3 Active Not Recruiting Treatment Irritability Associated With Autism Spectrum Disorder (ASD) 1 3 Completed Diagnostic Major Depressive Disorder (MDD) 1 3 Completed Treatment Acute Mania / Bipolar 1 Disorder 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 0.25 mg/1 Tablet, film coated Oral 0.5 mg/1 Tablet, film coated Oral 1 mg/1 Tablet, film coated Oral 2 mg/1 Tablet, film coated Oral 3 mg/1 Tablet, film coated Oral 4 mg/1 Kit; tablet Oral Tablet Oral 0.25 mg/1 Tablet Oral 0.25 mg Tablet Oral 0.5 mg/1 Tablet Oral 0.5 mg Tablet Oral 1 mg/1 Tablet Oral 1 mg Tablet Oral 2 mg Tablet Oral 2 mg/1 Tablet Oral 3 mg/1 Tablet Oral 3 mg Tablet Oral 3.000 mg Tablet Oral 4 mg/1 Tablet Oral 4 mg Tablet, film coated Oral 0.25 MG Tablet, film coated Oral 0.5 MG Tablet, film coated Oral 1 MG Tablet, film coated Oral 2 MG Tablet, film coated Oral 3 MG Tablet, film coated Oral 4 MG Tablet, coated Oral 0.25 mg Tablet, coated Oral 0.5 mg Tablet, coated Oral 1 mg Tablet, coated Oral 2 mg Tablet, coated Oral 3 mg Tablet, coated Oral 4 mg Tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8349840 No 2013-01-08 2026-04-12 US US8618109 No 2013-12-31 2026-04-12 US US7888362 No 2011-02-15 2027-02-23 US US9839637 No 2017-12-12 2026-04-12 US US10307419 No 2019-06-04 2032-10-12 US USRE48059 No 2020-06-23 2026-04-12 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 135.1 https://www.axonmedchem.com/media/certificates/2335-MSDS-B1.pdf boiling point (°C) 675.2 https://file.medchemexpress.com/batch_PDF/HY-15780/Brexpiprazole-SDS-MedChemExpress.pdf - Predicted Properties
Property Value Source Water Solubility 0.00227 mg/mL ALOGPS logP 5.38 ALOGPS logP 4.65 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 13.56 Chemaxon pKa (Strongest Basic) 8.4 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 44.81 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 129.16 m3·mol-1 Chemaxon Polarizability 49.48 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- 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
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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
- 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
- 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
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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]
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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]
- 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]
- Greig SL: Brexpiprazole: First Global Approval. Drugs. 2015 Sep;75(14):1687-97. doi: 10.1007/s40265-015-0462-2. [Article]
- 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
- 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
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
- 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
- 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
- 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