| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Targets |
Serotonin (5-HT) and Dopamine Receptors. Brexpiprazole acts as a partial agonist at human 5-HT1A (Ki = 0.12 nM) and dopamine D2L receptors (Ki = 0.3 nM). It is also an antagonist at 5-HT2A receptors (Ki = 0.47 nM), and has high affinity for human noradrenergic alpha1B (Ki = 0.17 nM) and alpha2C receptors (Ki = 0.59 nM). This unique receptor activity profile (serotonin-dopamine activity modulator, SDAM) yields antipsychotic effects with reduced side effects.
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|---|---|
| ln Vitro |
Brexpiprazole exhibits high affinity (<1 nM Ki) for 5-HT1A, 5-HT2A, dopamine D2L, and alpha1B- and alpha2C-adrenergic receptors in CHO cell membranes expressing human receptors. It is a partial agonist at 5-HT1A (EC50 = 0.49 nM, intrinsic activity 0.69) and a full antagonist at 5-HT2A. The D8-labeled analog is assumed to have equivalent receptor binding and functional properties, making it an ideal analytical internal standard.
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| ln Vivo |
In rodent models of antipsychotic activity (e.g., conditioned avoidance response, CAR), oral Brexpiprazole (0.1-3 mg/kg) potently suppresses avoidance behavior (minimal effective dose ~0.1 mg/kg), indicating D2 receptor antagonism in the nucleus accumbens. It also shows lower propensity for catalepsy (a measure of extrapyramidal symptoms, EPS) compared to haloperidol, suggesting a better motor side-effect profile.
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| Enzyme Assay |
Radioligand binding assays are performed using membrane preparations from CHO cells expressing human 5-HT1A, 5-HT2A, or D2L receptors. Membranes (20-50 microg protein) are incubated with appropriate radioligands ([3H]8-OH-DPAT for 5-HT1A, [3H]ketanserin for 5-HT2A, [3H]spiperone for D2L) and varying concentrations of Brexpiprazole D8 (0.001-1000 nM) in 50 mM Tris-HCl buffer (pH 7.4) for 60-90 min at 25degC. Nonspecific binding is determined with 10 microM unlabeled ligand (e.g., serotonin or haloperidol). Bound radioactivity is separated by filtration through GF/B filters and counted.
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| Cell Assay |
CHO cells expressing human 5-HT1A receptors are seeded in 96-well plates (50,000 cells/well) and loaded with Fluo-4 AM for calcium flux assays. Cells are pre-incubated with varying concentrations of Brexpiprazole D8 (0.01-1000 nM) for 30 min. The EC50 for partial agonism at 5-HT1A is determined by measuring the decrease in forskolin-stimulated cAMP accumulation using a competitive HTRF assay (Cisbio Dynamic Kit). For D2L antagonism, cells are stimulated with dopamine (30 nM) and the inhibition of cAMP accumulation is measured.
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| Animal Protocol |
Male Sprague-Dawley rats (250-300 g) are used. Brexpiprazole D8 is formulated in 0.5% methylcellulose. Animals receive a single oral dose of Brexpiprazole (0.3-10 mg/kg). At various time points (0.5, 1, 2, 4, 8, 12, 24, 48 h post-dose), blood samples are collected via tail vein or cardiac puncture under anesthesia. Plasma is separated, protein precipitated with acetonitrile, and analyzed by LC-MS/MS using Brexpiprazole D8 as the internal standard for quantification.
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| ADME/Pharmacokinetics |
Brexpiprazole D8 is used as an internal standard (IS) for LC-MS/MS quantification. The parent drug brexpiprazole has a long terminal half-life (~91 h in humans), allowing for once-daily dosing. It is highly protein bound (>99%), primarily to albumin and alpha1-acid glycoprotein. It is extensively metabolized by CYP3A4 and CYP2D6 to major metabolites (DM-3411, DM-3414). The parent drug and its metabolites are slowly eliminated.
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| Toxicity/Toxicokinetics |
The D8-labeled compound is for research use only. Brexpiprazole generally causes less weight gain, sedation, and metabolic syndrome than other atypical antipsychotics. Common AEs (≥5%): akathisia (restlessness), weight gain, and somnolence (sedation). Less common: extrapyramidal symptoms (EPS), gastrointestinal distress (nausea, constipation), and increased prolactin levels. Rare: neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), and metabolic changes.
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| References | |
| Additional Infomation |
Brexpiprazole (Rexulti) was FDA-approved in 2015 for adjunctive treatment of major depressive disorder (MDD) and for the treatment of schizophrenia. The D8-labeled version is a research internal standard for LC-MS/MS bioanalysis, used in pharmacokinetic studies (PK), therapeutic drug monitoring (TDM), and drug-drug interaction investigations, particularly involving CYP3A4 and CYP2D6 polymorphisms.
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| Molecular Formula |
C25H19D8N3O2S
|
|---|---|
| Molecular Weight |
441.6143
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| Exact Mass |
441.232
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| CAS # |
1427049-21-5
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| Related CAS # |
Brexpiprazole;913611-97-9
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| PubChem CID |
73160133
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
675.2±55.0 °C at 760 mmHg
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| Flash Point |
362.1±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
5.82
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XRRHXNKGLZWHRU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H35N3O2S/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/h3-5,10,17,19-20,22H,1-2,6-9,11-16,18H2,(H,26,29)
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| Chemical Name |
7-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy]-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-2-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2644 mL | 11.3222 mL | 22.6444 mL | |
| 5 mM | 0.4529 mL | 2.2644 mL | 4.5289 mL | |
| 10 mM | 0.2264 mL | 1.1322 mL | 2.2644 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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