药物化合物包括碳、氢和其他元素的稳定重同位素，在药物开发过程中主要作为定量示踪剂。由于氘化可能会影响药物的药代动力学和代谢特性，因此值得关注[1]。

Absorption, Distribution and Excretion
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. A high-fat meal did not significantly affect the Cmax or AUC of brexpiprazole.
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.
The volume of distribution of brexpiprazole following intravenous administration is 1.56 ± 0.42 L/kg, indicating extravascular distribution.
Apparent oral clearance of brexpiprazole after once-daily administration is 19.8 (±11.4) mL/h/kg.

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Metabolism / Metabolites
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.

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Biological 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.

Hepatotoxicity
Liver test abnormalities were reported to occur in ~1% of patients on long term therapy with brexpiprazole, but similar rates occurred in patients on placebo or with comparator agents. There have been no published reports of clinically apparent acute liver injury due to brexpiprazole and only rare instances have been reported with the much more frequently used aripiprazole. Thus, liver injury due to brexpiprazole must be rare, if it occurs at all.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the excretion of brexpiprazole in breastmilk. A single case report implicated brexpiprazole as a cause of decreased lactation. A review of case reports found lactation disorders and breast secretion reported as side effects, but details are lacking. Until more data are available, an alternate drug may be preferred.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
A woman was taking brexpiprazole 2 mg daily during the third trimester of pregnancy for bipolar disorder. Her newborn infant was hospitalized in the NICU for hypoxic ischemic encephalopathy for 18 days. While her infant was in the NICU, she reduced her brexpiprazole dose to 2 mg every 2 days because of a shortage of medication. The mother, who had successfully breastfed 2 previous infants, pumped milk 10 times daily and was able to pump 120 mL daily by one week postpartum. After her infant was discharged, she increased the dose back to 2 mg daily. At a follow-up clinic visit, she could only pump 30 mL daily. She then stopped brexpiprazole and began a short course of metoclopramide. Within 10 days of stopping brexpiprazole, her milk supply increased, and she could almost exclusively breastfeed her infant who gained weight normally. Her serum prolactin level also increased to normal.
A review of case reports of adverse reactions reported in the US Food and Drug Administration’s Adverse Event Reporting System from 2015 to 2023 found 6 reports of “lactation disorder” and 10 cases of “breast discharge” reported with brexpiprazole. Other details were lacking.

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Protein Binding
_In vitro_, brexpiprazole was 99% bound to plasma proteins, mainly serum albumin and α1-acid glycoprotein.

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.

[2]. Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors. Eur Neuropsychopharmacol. 2015 Apr;25(4):505-11.

[3]. Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamine activity modulator. Eur Neuropsychopharmacol. 2015 Mar;25(3):356-64.

Brexpiprazole is a N-arylpiperazine.
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. 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. Brexpiprazole was first approved by the FDA on July 10, 2015. 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.
Brexpiprazole is an Atypical Antipsychotic.
Brexpiprazole is an atypical antipsychotic used in the treatment of schizophrenia and major depressive disorders. Brexpiprazole has been associated with a low rate of serum aminotransferase elevations during therapy but has not been linked to instances of clinically apparent acute liver injury.

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

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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-HT_1A and dopamine D2 receptors, and antagonist activity at 5-HT_2A receptors. Brexpiprazole binds to these receptors with subnanomolar affinities. 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-HT_1A receptors may be tied to improved memory function and cognitive performance. Antagonism at α-adrenergic receptors has also been implicated in schizophrenia and depression.

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Pharmacodynamics
Brexpiprazole is an atypical antipsychotic agent used to ameliorate the symptoms of psychiatric conditions, such as cognitive deficits and affective symptoms. Brexpiprazole has affinity (expressed as Ki) for multiple monoaminergic receptors including serotonin 5-HT_1A (0.12 nM), 5-HT_2A (0.47 nM), 5-HT_2B (1.9 nM), 5-HT₇ (3.7 nM), dopamine D2 (0.30 nM), D3 (1.1 nM), and noradrenergic α_1A (3.8 nM), α_1B (0.17 nM), α_1D (2.6 nM), and α_2C (0.59 nM) receptors. Brexpiprazole acts as a partial agonist at the 5-HT_1A, D2, and D3 receptors and as an antagonist at 5-HT_2A, 5-HT_2B, 5-HT₇, α_1A, α_1B, α_1D, and α_2C receptors. Brexpiprazole also exhibits affinity for histamine H1 receptor (19 nM) and for muscarinic M1 receptor (67% inhibition at 10 µM).

C25H27N3O2S

441.615078210831

433.182

1427049-19-1

Brexpiprazole;913611-97-9

11978813

Off-white to light yellow solid powder

4.7

73

1

5

7

31

636

0

S1C=CC2=C1C=CC=C2N1C([2H])([2H])C([2H])([2H])N(CCCCOC2=CC=C3C=CC(NC3=C2)=O)C([2H])([2H])C1([2H])[2H]

ZKIAIYBUSXZPLP-UHFFFAOYSA-N

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)

7-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy]-1H-quinolin-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。