 | |
 | |
| Clinical data | |
|---|---|
| Pronunciation | /brɛkˈspɪprəzoʊl/brek-SPIP-rə-zohl |
| Trade names | Rexulti, Rxulti, others |
| Other names | OPC-34712 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a615046 |
| License data | |
| Pregnancy category | |
| Routes of administration | By mouth |
| Drug class | Atypical antipsychotic |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 95% (Tmax = 4 hours)[10] |
| Protein binding | >99% |
| Metabolism | Liver (mainly mediated byCYP3A4 andCYP2D6) |
| Eliminationhalf-life | 91 hours (brexpiprazole), 86 hours (major metabolite) |
| Excretion | Feces (46%), urine (25%) |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.242.305 |
| Chemical and physical data | |
| Formula | C25H27N3O2S |
| Molar mass | 433.57 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Brexpiprazole, sold under the brand nameRexulti among others, is anatypical antipsychotic medication used for the treatment ofmajor depressive disorder,schizophrenia, andagitation associated with dementia due toAlzheimer's disease.[10][12][13]
The most common side effects includeakathisia (a constant urge to move) and weight gain.[11] The most common side effects among people with agitation associated with dementia due to Alzheimer's disease include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances (both somnolence and insomnia).[12]
Brexpiprazole was developed byOtsuka andLundbeck, and is considered to be a successor toaripiprazole (Abilify).[14] It was approved for medical use in the United States in July 2015.[15][16] Ageneric version was approved in August 2022.[17] Brexpiprazole is the first treatment approved by the USFood and Drug Administration (FDA) for agitation associated with dementia due to Alzheimer's disease.[12]
In the United States and Canada, brexpiprazole isindicated as an adjunctive therapy to antidepressants for the treatment of major depressive disorder and for the treatment of schizophrenia.[7][10][18][19] In May 2023, the indication for brexpiprazole was expanded in the US to include the treatment of agitation associated with dementia due to Alzheimer's disease.[12]
In Australia and the European Union, brexpiprazole is indicated for the treatment of schizophrenia.[2][11]
In 2020, it was approved in Brazil only as an adjunctive to the treatment of major depressive disorder.[20][21]
The most common adverse events associated with brexpiprazole (all doses of brexpiprazole cumulatively greater than or equal to 5% vs. placebo) wereupper respiratory tract infection (6.9% vs. 4.8%),akathisia (6.6% vs. 3.2%),weight gain (6.3% vs. 0.8%), andnasopharyngitis (5.0% vs. 1.6%).[22] Brexpiprazole can cause impulse control disorders.[23]
 | This sectionmay beconfusing or unclear to readers. In particular, it has poor grammar and too many parentheticals. Please helpclarify the section. There might be a discussion about this onthe talk page.(May 2025) (Learn how and when to remove this message) |
It exerts its pharmacodynamic actions mainly by modulating signaling of multiple serotonin, dopamine and noradrenaline receptors.
| Site | Human Ki (nM) | IA (%) | Action | Ref |
|---|---|---|---|---|
| SERTTooltip Serotonin transporter | 65% at 10 μM | Blocker | [25] | |
| NETTooltip Norepinephrine transporter | 0% at 10 μM | Blocker | [25] | |
| DATTooltip Dopamine transporter | 90% at 10 μM | Blocker | [25] | |
| 5-HT1A | 0.12 | ~60% | Partial agonist | [25] |
| 5-HT1B | 32 | ND | [25] | |
| 5-HT2A | 0.47 | Antagonist | [25] | |
| 5-HT2B | 1.9 | Antagonist | [25] | |
| 5-HT2C | 34 | Antagonist | [25] | |
| 5-HT5A | 140 | ND | [25] | |
| 5-HT6 | 58 | Antagonist | [25] | |
| 5-HT7 | 3.7 | Antagonist | [25] | |
| D1 | 160 | ND | [25] | |
| D2L | 0.30 | ~45% | Partial agonist | [25] |
| D3 | 1.1 | ~15% | Partial agonist | [25] |
| D4 | 6.3 | ND | [25] | |
| D5 | 66% at 1 μM | ND | ND | |
| α1A | 3.8 | Antagonist | [25] | |
| α1B | 0.17 | Antagonist | [25] | |
| α1D | 2.6 | Antagonist | [25] | |
| α2A | 15 | Antagonist | [25] | |
| α2B | 17 | Antagonist | [25] | |
| α2C | 0.59 | Antagonist | [25] | |
| β1 | 59 | Antagonist | [25] | |
| β2 | 67 | Antagonist | [25] | |
| β3 | >10,000 | ND | [25] | |
| H1 | 19 | Antagonist | [25] | |
| H2 | >10,000 | ND | [25] | |
| H3 | >10,000 | ND | [25] | |
| mAChTooltip Muscarinic acetylcholine receptor | 52% at 10 μM | ND | [25] | |
| M1 | 67% at 10 μM | ND | [25] | |
| M2 | >10,000 | ND | [25] | |
| σ | 96% at 10 μM | ND | [25] | |
| Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. Most or all data are for human cloned proteins. IA = Intrinsic Activity | ||||
Brexpiprazole acts as apartial agonist of theserotonin5-HT1A receptor and thedopamineD2 andD3 receptors.[25] Brexpiprazole is a less stimulating partial agonist of the dopamine receptors than its predecessor,aripiprazole, potentially decreasing its risk for agitation and restlessness.[25] Brexpiprazole has a high affinity for the5-HT1A receptor, acting as a potent antagonist at 5-HT2A receptors, and a potent partial agonist at dopamine D2 receptors with lower intrinsic activity compared toaripiprazole.[28][29]In vivo characterization of brexpiprazole shows that it may act as a near-full agonist of the5-HT1A receptor. This may further underlie a lower potential than aripiprazole to cause treatment-emergent, movement-related disorders such as akathisia due to the downstream dopamine release that is triggered by5-HT1A receptor agonism. It is also anantagonist of the serotonin5-HT2A,5-HT2B, and5-HT7 receptors, which may contribute to antidepressant effect. It also binds to and blocks theα1A-,α1B-,α1D-, andα2C-adrenergic receptors.[25] The drug has negligibleaffinity for themuscarinic acetylcholine receptors, and hence has noanticholinergic effects.[25] Although brexpiprazole has less affinity forH1 compared toaripiprazole, weight gain can occur.[30]
Brexpiprazole was in clinical trials for adjunctive treatment ofmajor depressive disorder,adult attention deficit hyperactivity disorder,bipolar disorder,[31]schizophrenia,[32] and agitation associated with dementia due to Alzheimer's disease.[12]
The phase II multicenter, double-blind, placebo-controlled study randomized 429 adult MDD patients who exhibited an inadequate response to one to three approved antidepressant treatments (ADTs) in the current episode. The study was designed to assess the efficacy and safety of brexpiprazole as an adjunctive treatment to standard antidepressant treatment. The antidepressants included in the study weredesvenlafaxine,escitalopram,fluoxetine,paroxetine,sertraline, andvenlafaxine.[33]
A phase III study was in the recruiting stage: "Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)".[34] Its goal is "to compare the effect of brexpiprazole to the effect of placebo (an inactive substance) as add on treatment to an assigned FDA approved antidepressant treatment (ADT) in patients withmajor depressive disorder who demonstrate an incomplete response to a prospective trial of the same assigned FDA approved ADT". Estimated enrollment was 1250 volunteers.
The effectiveness of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease was determined through two 12-week, randomized, double-blind, placebo-controlled, fixed-dose studies.[12] In these studies, participants were required to have a probable diagnosis of Alzheimer's dementia; have a score between 5 and 22 on the Mini-Mental State Examination, a test that detects whether a person is experiencing cognitive impairment; and exhibit the type, frequency, and severity of agitation behaviors that require medication.[12] Trial participants ranged between 51 and 90 years of age.[12]
In January 2018, it was approved for the treatment ofschizophrenia in Japan.[42]
In November 2011,Otsuka Pharmaceutical andLundbeck announced a global alliance.[43]
Brexpiprazole was under development for the treatment ofattention deficit hyperactivity disorder (ADHD) as anadjunct tostimulants, but was discontinued for this indication.[45][46][47] It reachedphase IIclinical trials for this use prior to discontinuation.[47]
Brexpiprazole has shown promise in clinical trials for the treatment ofborderline personality disorder.[48]
This article incorporates text from this source, which is in thepublic domain.
Media related toBrexpiprazole at Wikimedia Commons