5-HT_1A Receptor; 5-HT_2A Receptor; 5-HT_2B Receptor; 5-HT_2C Receptor; D₂ Receptor; D₃ Receptor; D₄ Receptor

阿立哌唑一水合物可有效激活 D2 受体介导的 cAMP 积累抑制作用[1]。阿立哌唑一水合物对 TNF-α、IL-13、IL-17α 和 fractalkine 显示出更强的抗炎作用[3]。

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体外活性：阿立哌唑以高亲和力与 G 蛋白偶联和非偶联状态的受体结合。阿立哌唑可有效激活 D2 受体介导的 cAMP 积累抑制作用。阿立哌唑对 h5-HT(2B)-、hD(2L)- 和 hD(3)- 多巴胺受体具有最高的亲和力，但对其他几种 5-HT 受体 (5-HT) 也具有显着的亲和力 (5-30 nM) (1A)、5-HT(2A)、5-HT(7))，以及 α(1A)-肾上腺素能受体和 hH(1)-组胺受体。阿立哌唑对其他 G 蛋白偶联受体的亲和力较低 (30-200 nM)，包括 5-HT(1D)、5-HT(2C)、α(1B)-、α(2A)-、α(2B) -、α(2C)-、β(1)-、β(2)-肾上腺素能受体和 H(3)-组胺受体。阿立哌唑是 5-HT(2B) 受体的反向激动剂，并对 5-HT(2A)、5-HT(2C)、D(3) 和 D(4) 受体显示部分激动作用。

阿立哌唑一水合物（0-3 mg/kg，腹腔注射，每日）显示出一些抗焦虑特性[4]。动物模型：WAG/Rij 大鼠（每剂 N = 6 只，6 个月，给予替来他明/唑拉西泮混合物）[4] 剂量：0、0.3、1、3 mg/kg 给药方式：腹膜内注射，1 mL/kg，每天下午 5 点直至实验结束 结果：显示出一定的抗焦虑特性，其中 1 mg/kg 剂量最为有效。

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阿立哌唑（APZ）被认为是一线非典型抗精神病药物，用于治疗首次和多次发作的精神分裂症，以改善阳性和阴性症状。其治疗适应症扩展到急性躁狂和与双相情感障碍相关的混合发作。此外，APZ在2007年被批准作为重度抑郁症的辅助治疗。与其他抗精神病药物相比，APZ具有独特的药理特征。它是D₂多巴胺受体和5-羟色胺5-HT（1A）和5-HT₇受体的部分激动剂，而它是5-羟色胺5-HT（2A）和5-HT₆受体的拮抗剂。由于癫痫通常伴有神经系统合并症，如疾病和/或药物治疗引起的抑郁、焦虑和认知缺陷，我们希望研究亚慢性治疗（>14连续天）使用APZ(0.3、1和3 mg/kg；使用不同的标准范式：开放场（OF）测试、升高加迷宫（EPM）测试、强迫游泳（FS）测试、蔗糖消耗（SC）测试和Morris水迷宫（MWM）测试，对失神发作和WAG/Rij大鼠的行为进行了研究。WAG/Rij大鼠代表了一种经过验证的伴有轻度抑郁共病的缺失性癫痫的遗传动物模型，也包括其他行为改变。对于该品系的行为共病，我们观察到APZ在FS和SC测试中具有明显的抗抑郁作用，并在Morris水迷宫测试中提高了记忆/学习功能。在使用的两种焦虑模型中，APZ仅显示出轻微的影响。综上所述，我们的研究结果表明，APZ实际上可能在治疗失神性癫痫或作为附加治疗方面具有潜力，但更有趣的是，这些作用可能伴随着对抑郁、焦虑和记忆的积极调节作用，这也可能对其他癫痫综合征有益。本文是“认知增强剂”特刊的一部分。[4]

放射性配体结合试验[2]
大量瞬时和稳定转染的克隆人类cdna，通过国家精神卫生研究所精神活性药物筛选计划（NIMH-PDSP）的资源获得，用于放射配体结合和功能分析，如前面所述(Rothman等人，2000；Tsai et al ., 2000)。表1列出了放射配体结合测定的条件，以及标准化合物的KD值。在初始筛选试验中，以10 μM的浓度对大量gpcr、离子通道和转运体进行了阿立哌唑四次重复的测试。对于>50%抑制的分子靶点，使用至少6个浓度<强>阿立哌唑的浓度来测定Ki；使用GraphPad Prism计算四份Ki值。[125I]DOI竞争试验按照前面的描述进行（Choudhary等，1992），并做了以下改变：将12个阿立哌唑的稀释度，范围为0.01-3000 nM，与[125I]DOI （0.3 nM）在25°C下，以总体积为0.25 ml，结合缓冲液（50 mM Tris缓冲液，pH 7.4, 0.5 mM EDTA, 10 mM MgCl2）中5-20 μg的膜蛋白孵育1小时。用Brandel细胞收割机在聚乙烯亚胺预处理（0.3%）Whatman GF/C过滤器上进行三次冷水洗涤，收获膜。结合滤光片的放射性是用液体闪烁计数来量化的。

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阿立哌唑是第一个下一代非典型抗精神病药，其作用机制不同于目前上市的典型和非典型抗精神病药。阿立哌唑分别在多巴胺能低活性和多活性动物模型中表现出激动剂和拮抗剂的特性。本研究检测了阿立哌唑与单一人群D2受体的相互作用，以进一步阐明其药理学特性。在表达重组D2L受体的中国仓鼠卵巢细胞制备的膜中，阿立哌唑对G蛋白偶联和非偶联状态的受体都具有高亲和力。阿立哌唑有效激活D2受体介导的cAMP积累抑制。用烷基化剂n -乙氧羰基-2-乙氧基-1,2-二氢喹啉（EEDQ）灭活部分受体显著降低了阿立哌唑抑制cAMP积累的最大效果。这种效应是在EEDQ浓度不改变多巴胺最大抑制作用的情况下观察到的。与部分激动剂的预期作用一致，增加阿立哌唑浓度阻断多巴胺的作用，其最大阻断作用相当于单独使用阿立哌唑的激动剂作用。阿立哌唑相对于多巴胺的疗效在缺乏多巴胺备用受体的细胞中为25%，在具有受体储备的细胞中为90%。这些结果，连同先前的研究表明部分激动剂对5-羟色胺（5-HT）1A受体的活性和拮抗剂对5-HT2A受体的活性，支持阿立哌唑作为多巴胺- 5-羟色胺系统稳定剂的鉴定。受体活性谱可能是阿立哌唑在动物体内的独特活性及其在人类中的抗精神病活性的基础。［2］

阿立哌唑对cAMP生成的影响[2]
福斯克林刺激cAMP生成的抑制作用[2]
如先前报道的那样，在稳定的D4和5- ht1a受体表达细胞系中测量了福斯克林刺激的3 ‘,5 ’环腺苷单磷酸（cAMP）产生的抑制作用(Lawler等，1999；Zhang et al ., 1994)。简单地说，在24孔板中培养细胞，在实验之前用含有100 μM IBMX和100 μM forskolin（全部在冰上）的新鲜F12培养基替换生长培养基。在细胞中加入10倍稀释的阿立哌唑 0.1 ~ 10.000 nM，然后在37℃和5% CO2下孵育20 min。通过抽吸和加入0.5 ml的3%三氯乙酸来终止反应。4℃冷冻1 h， 1000 g旋转15 min。cAMP采用竞争性结合测定法进行了少量修改（Nordstedt和Fredholm， 1990）。测定cAMP含量时，将三氯乙酸提取物（40 μl）加入到含有cAMP测定缓冲液（100 mM Tris-HCl, pH 7.4, 100 mM NaCl, 5 mM EDTA）的反应管中。[3H]每管加入终浓度为1 nM的cAMP，然后加入cAMP结合蛋白（500 μl cAMP缓冲液中约100 μg牛肾上腺皮质粗提物）。反应管在冰上孵育2小时，然后用Brandel细胞收集机收获到浸泡在水中的Whatman GF/C过滤器上。滤光片干燥，结合放射性通过液体闪烁计数来量化。每个样品中cAMP的浓度从0.1至100 pmol /assay的标准曲线估计。

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刺激cAMP产量[2]
使用先前描述的方法在稳定的转染物中研究了5-HT6和5-HT7受体中血清素和阿立哌唑的作用(Max等人，1995；Monsma et al ., 1993；Shen et al ., 1993)。

WAG/Rij rats (N = 6 per dose, 6 months, administration of a mixture of tiletamine/zolazepam)
0, 0.3, 1, 3 mg/kg
IP, 1 mL/kg, every day at 5 p.m. until the end of the experiments

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Sub-chronic treatment procedure [4]
Aripiprazole (APZ) was dispersed in a 1% aqueous solution (physiological saline) of Tween 80. Rats were treated intraperitoneally (i.p.) with APZ at the doses of 0.3, 1 and 3 mg/kg in a volume of 1 ml/kg injected every day at 5 p.m. until the end of the experiments. To evaluate the effects of a short-term APZ treatment (sub-chronic) on absence seizures, different groups of rats, around 6 months of age, were treated for 14 consecutive days, starting treatment one week after surgery for electrode implantation (see Section 2.3). Starting on the 15th day, rats of the sub-chronic treatment group (absence seizure evaluation) underwent three recording periods as described in Section 2.3; treatment was continued up to the last day of recordings. Control group received equal volumes of vehicle (1% Tween 80 in physiological saline). Relative to behavioral tests, no surgery was performed and treatment was continued as above reported for the entire duration of the tests without discontinuation. Therefore, the drug was always present in the system at the moment of the test. Total duration of the treatment in every test should be considered as 14 days added to day of testing; i.e. in the Morris water maze test, on day 5 recordings animals were treated for 19 consecutive days (14 + 5). In any case, APZ blood concentration can be considered stable being at the steady-state already before testing being its half-life in rats is about 1 h.

Absorption, Distribution and Excretion
Tablet: Aripiprazole is well absorbed after administration of the tablet, with peak plasma concentrations occurring within 3 hours to 5 hours; the absolute oral bioavailability of the tablet formulation is 87%. ABILIFY can be administered with or without food. Administration of a 15 mg ABILIFY tablet with a standard high-fat meal did not significantly affect the Cmax or AUC of aripiprazole or its active metabolite, dehydro-aripiprazole, but delayed Tmax by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole. Oral Solution: Aripiprazole is well absorbed when administered orally as the solution. At equivalent doses, the plasma concentrations of aripiprazole from the solution were higher than that from the tablet formulation. In a relative bioavailability study comparing the pharmacokinetics of 30 mg aripiprazole as the oral solution to 30 mg aripiprazole tablets in healthy subjects, the solution-to-tablet ratios of geometric mean Cmax and AUC values were 122% and 114%, respectively. The single-dose pharmacokinetics of aripiprazole were linear and dose-proportional between the doses of 5 mg to 30 mg. Extended-release injectable suspension, bimonthly injection: Aripiprazole absorption into the systemic circulation is prolonged following gluteal intramuscular injection due to the low solubility of aripiprazole particles. The release profile of aripiprazole from ABILIFY ASIMTUFII results in sustained plasma concentrations over 2 months following gluteal injection(s). Following multiple doses, the median peak:trough ratio for aripiprazole following an ABILIFY ASIMTUFII dose is 1.3, resulting in a flat plasma concentration profile with Tmax ranging between 1 to 49 days following multiple gluteal administrations of 960 mg.
Following a single oral dose of [14C]-labeled aripiprazole, approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.
The steady-state volume of distribution of aripiprazole following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution.
The clearance of aripiprazole was estimated to be 0.8mL/min/kg. Other studies have also reported a clearance rate of 3297±1042mL/hr.
Oral availability 87%. Aripiprazole is well absorbed and can be administered with or without food. Administration with a high fat meal did not affect the Cmax or AUC, but delayed Tmax by 3 hours for aripiprazole, and 12 hours for dehydro-aripiprazole.
Time to peak concentration: Peak plasma concentrations: within 3 to 5 hours.
The steady-state volume of distribution of aripiprazole following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole and its major metabolite are greater than 99% bound to serum proteins, primarily to albumin.
There was dose-dependent D2-receptor occupancy indicating brain penetration of aripiprazole in healthy human volunteers administered 0.5 to 30 mg per day.
For more Absorption, Distribution and Excretion (Complete) data for ARIPIPRAZOLE (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for the dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4. Aripiprazole is the predominant drug moiety in systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.
Aripiprazole is extensively metabolized in the liver principally via dehydrogenation, hydroxylations, and N-dealkylation by the cytochrome P-450 (CYP) 2D6 and 3A4 isoenzymes. The major active metabolite of aripiprazole, dehydro-aripiprazole, exhibits affinity for D2 receptors similar to that of the parent compound and represents approximately 40% of the aripiprazole area under the concentration-time curve (AUC) in plasma. Steady-state plasma concentrations of both aripiprazole and dehydro-aripiprazole are achieved within 14 days.
ABILIFY activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma.
Aripiprazole has known human metabolites that include dehydro-aripiprazole, 4-[(2-oxo-3,4-dihydro-1H-quinolin-7-yl)oxy]butanal, 4-Hydroxyaripiprazole, and 2,3-dichlorophenylpiperazine.
Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation,and N-dealkylation.Based on in vitro studies,CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4.Aripiprazole is the predominant drug moiety in the systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma (RxList, A308).
Route of Elimination: Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.
Half Life: 75-146 hours

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Biological Half-Life
The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. For populations that are poor CYP2D6 metabolizers, the half-life of aripiprazole is 146 hours and these patients should be treated with half the normal dose. Other studies have reported a half-life of 61.03±19.59 hours for aripiprazole and 279±299 hours for the active metabolite.
The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively.

Hepatotoxicity
Liver test abnormalities have not been reported to occur in patients on long term therapy with aripiprazole, but most studies have not provided information on serum enzyme results. Despite its widescale use, aripiprazole has been implicated in only rare and isolated cases of clinically apparent liver injury in the literature. All reported cases have been hepatocellular arising after 1 to 3 months of therapy and with accelerated onset in one instance upon re-exposure. Immunoallergic and autoimmune features were not present. Most cases have been anicteric, and none were fatal or resulted in chronic injury. Aripiprazole has not been reported among agents implicated in large case series of drug induced liver injury. The product label for aripiprazole mentions that hepatitis and jaundice have been reported, but no specific details were provided. Thus, clinically apparent liver injury from aripiprazole must be very rare.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that maternal doses of aripiprazole up to 15 mg daily produce low levels in milk. Aripiprazole can lower serum prolactin in a dose-related manner. Cases of lactation cessation have occurred, but cases of gynecomastia and galactorrhea have also been reported. Weight loss and poor weight gain have been reported in breastfed infants whose mothers were taking aripiprazole. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
A woman took aripiprazole 15 mg daily by mouth during pregnancy and postpartum. She breastfed her infant (amount not stated) and at 3 months of age, the infant was growing normally.
A woman took aripiprazole 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. She exclusively breastfed her infant for 6 weeks, then was partially breastfed. At 4 months of age the infant was still breastfeeding and had normal psychomotor and behavioral development and had reached the expected milestones for her age.
A 12-day-old exclusively breastfed male infant presented with severe weight loss and hypernatremic dehydration because of inadequate milk intake and a 30% weight loss since birth. The infant's mother was being treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. She was also taking levothyroxine 50 mcg once daily, a prenatal multivitamin, and folic acid. On initial evaluation in the emergency department, he was pale, with marbled skin, dry mucous membranes, decreased skin turgor, and bluish feet with prolonged capillary refill. The right foot eventually became darker with blackened toes and he developed gangrene of the right lower limb, which did not respond to medical therapy and required amputation of all five toes and surgical debridement of the metatarsals. Necrosis was attributed to arterial microthrombi caused by disseminated intravascular coagulation after severe dehydration. The authors considered the mother's medications as a possible cause of the dehydration and related problems.
A woman with paranoid schizophrenia had been receiving long-acting injectable aripiprazole 400 mg every 28 days for 32 months when pregnancy was confirmed. The dose was lowered to 300 mg every 28 days and after delivery she breastfed her infant (extent and duration not stated). At 3 years of age, the infant’s growth and development were normal.
Patients enlisted in the National Pregnancy Registry for Atypical Antipsychotics who were taking a second-generation antipsychotic drug while breastfeeding (n = 576) were compared to control breastfeeding patients who were not treated with a second-generation antipsychotic (n = 818). Of the patients who were taking a second-generation antipsychotic drug, 60.4% were on more than one psychotropic. A review of the pediatric medical records, no adverse effects were noted among infants exposed or not exposed to second-generation antipsychotic monotherapy or to polytherapy. The number of women taking aripiprazole was not reported.
◉ Effects on Lactation and Breastmilk
Unlike the phenothiazines, aripiprazole has a minimal effect on serum prolactin levels and it has been used to reverse hyperprolactinemia in nonlactating patients taking other antipsychotics. Case reports of both decreased lactation in nursing mothers and cases of hyperprolactinemia and galactorrhea in patients taking aripiprazole have been reported. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.
One woman began taking aripiprazole 10 mg daily at week 20 of pregnancy. She underwent a cesarean section delivery at term, but was unable to establish lactation. The authors suggested that more data are needed to determine if aripiprazole adversely affects lactation.
A woman took aripiprazole 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. She exclusively breastfed her infant for 6 weeks, but then began supplementation because of insufficient milk production. Her serum prolactin was 35 to 40 mcg/L, which is lower than expected for a nursing mother. The authors speculated that the aripiprazole might have been the cause of her low serum prolactin and diminished her milk supply.
A woman with bipolar disorder was taking lithium during pregnancy and postpartum. At 10 days postpartum, her infant's serum lithium level was 0.26 mmol/L, so lithium was discontinued. Quetiapine was begun, but discontinued because of maternal sedation. Aripiprazole 2.5 mg daily was begun and within 24 hours, the mother noted a marked decrease in milk supply. After 2 weeks of working with a lactation consultant, she continued to have lactation difficulties and she switched back to lithium. Within 48 hours, her milk supply improved markedly.
A retrospective study of outpatients receiving an average aripiprazole dose of 17.3 mg daily (n = 20) or another antipsychotic (n = 141) found that those receiving such high-dose aripiprazole had an 81% chance of having hypoprolactinemia. Patients not treated with aripiprazole had only a 2.9% chance of having hypoprolactinemia.
The breastfeeding mother of a 5-week-old infant was diagnosed with bipolar disorder, panic attacks and anxiety disorder. She was started on hydroxyzine 50 mg at an unspecified interval and took it for 3 to 5 days with no effect on milk production. She then started on aripiprazole 5 mg at an unspecified interval. After 5 days, she reported a decrease in milk production that required supplementation with formula. Nine days after stopping both drugs, her milk supply returned to normal. The decreased milk supply was possibly caused by the medications, with aripiprazole most likely.
A woman with chronic depression was treated throughout pregnancy with extended-release venlafaxine 225 mg daily. She gave birth by cesarean section at 36.5 weeks and began to breastfeed her infant. The infant was not nursing adequately, but the mother pumped milk after each feeding and used it to supplement the infant. It was estimated that she was producing at least 900 mL of milk daily. By 8 days postpartum, she began to experience depression and aripiprazole 2 mg daily, which she had taken before pregnancy, was added to her regimen. After 3 days of combined therapy, she noticed a decrease in milk supply, and withing 21 days, lactation had ceased completely. Either aripiprazole or the combination with venlafaxine possibly caused a decrease in milk supply.
A woman with major depressive disorder received duloxetine 40 mg twice daily. After 2 weeks, she developed menstrual irregularities and a milky discharge from her breasts. Her serum prolactin was elevated at 205 mcg/L. The duloxetine dosage was decreased to 60 mg once daily and aripiprazole was begun at 2.5 mg daily and then increased to 5 mg daily. Within 2 weeks, galactorrhea had stopped and the serum prolactin had decreased to 118 mcg/L. Six weeks later, serum prolactin was 39 mcg/L. The combination was continued for another 39 weeks with no return of galactorrhea.
A postpartum woman was given sertraline 200 mg daily for anxiety, depressive symptoms, hypocondriform thoughts and checking compulsions, which interfered with bonding. Two months later aripiprazole 5 mg daily was added. Two to three days later the patient reported decreased milk production. Prolactin levels decreased from a previous 30.18 mcg/L to 5.02 mcg/L. Milk production normalized in less than a week after stopping aripiprazole.
Patients enlisted in the National Pregnancy Registry for Atypical Antipsychotics who were taking a second-generation antipsychotic drug while breastfeeding (n = 576) were compared to control breastfeeding patients who had primarily diagnoses of major depressive disorder and anxiety disorders, most often treated with SSRI or SNRI antidepressants, but not with a second-generation antipsychotic (n = 818). Among women on a second-generation antipsychotic, 60.4% were on more than one psychotropic compared with 24.4% among women in the control group. Of the women on a second-generation antipsychotic, 59.3% reported “ever breastfeeding” compared to 88.2% of women in the control group. At 3 months postpartum, 23% of women on a second-generation antipsychotic were exclusively breastfeeding compared to 47% of women in the control group. The number of women taking aripiprazole was not reported.
Two women took aripiprazole during pregnancy and postpartum for schizophrenia in doses of 10 and 20 mg daily. Neither mother could breastfeed her infant because of little to no milk production.
◈ What is aripiprazole?
Aripiprazole is medication that has been used to treat schizophrenia, bipolar disorder, autism spectrum disorders, and depression. Some brand names for aripiprazole include Abilify®, Abilify Discmelt®, Aristada®, and Abilify Maintena®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take your medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.For more information on depression, see our fact sheet at https://mothertobaby.org/fact-sheets/depression-pregnancy/.
◈ I take aripiprazole. Can it make it harder for me to get pregnant?
Studies have not been done to see if taking aripiprazole could make it harder to get pregnant.
◈ Does taking aripiprazole increase the chance of miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. It is not known if aripiprazole increases the chance of miscarriage. One study looking at the use of aripiprazole in pregnancy reported an increased chance of miscarriage, but other studies have not reported this finding. However, some studies have reported a higher chance of miscarriage when depression is left untreated in pregnancy. As there can be many causes of miscarriage, it is hard to know if a medication, the condition being treated, or other factors are the cause of a miscarriage.
◈ Does taking aripiprazole increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Information on the use of aripiprazole in pregnancy is limited. Three small studies and one large study did not show an increased chance of birth defects when aripiprazole was taken during pregnancy.
◈ Does taking aripiprazole in pregnancy increase the chance of other pregnancy-related problems?
It is not known if aripiprazole can cause other pregnancy-related problems, such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth). There are studies that reported a slightly increased chance of preterm birth and babies who were born smaller than expected. In these studies, aripiprazole was taken for a short time. However, the underlying illness being treated might also increase the chance of these pregnancy complications.
◈ I need to take aripiprazole throughout my entire pregnancy. Will it cause withdrawal symptoms in my baby after birth?
There have been reports of babies exposed to aripiprazole during late pregnancy who had symptoms soon after birth. These symptoms are sometimes referred to as withdrawal and can include jitteriness, breathing problems, shaking, sleepiness, eating problems, rigid muscles, or low muscle tone. Information on this is limited, and it is not known if the chance of this happening is high or low. In some babies the symptoms can go away quickly, while other babies might need treatment in the hospital. Not all babies exposed to aripiprazole will have these symptoms. It is important that your healthcare providers know you are taking aripiprazole so that if symptoms occur your baby can get the care that is best for them.
◈ Does taking aripiprazole in pregnancy affect future behavior or learning for the child?
It is not known if aripiprazole increases the chance of behavior or learning issues for the child. However, the underlying illness being treated might also affect a child’s behavior or development.
◈ Breastfeeding while taking aripiprazole:
A limited number of studies have shown that when a person who is breastfeeding takes up to 15mg of aripiprazole a day, the medication passes into breastmilk in small amounts. While there have been cases of babies becoming sleepier than usual, most breastfed babies exposed to aripiprazole have no reported symptoms. If you suspect the baby has any symptoms, (such as being too sleepy or having trouble eating), contact the child’s healthcare provider right away.Aripiprazole may lower the amount of milk your body makes. Be sure to talk to your healthcare provider about all your breastfeeding questions.
◈ If a male takes aripiprazole, could it affect fertility or increase the chance of birth defects?
Studies have not been done to see if aripiprazole could affect male fertility (ability to get partner pregnant) or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
At therapeutic concentrations, aripiprazole and its major metabolite are greater than 99% bound to serum proteins, primarily to albumin.

[1]. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002 Jul;302(1):381-9.

[2]. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003 Aug;28(8):1400-11.

[3]. Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis. Front Pharmacol. 2021 Mar 2;12:646701.

[4]. Ameliorating effects of aripiprazole on cognitive functions and depressive-like behavior in a genetic rat model of absence epilepsy and mild-depression comorbidity. Neuropharmacology. 2013 Jan;64:371-9.

[5]. Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology. CNS Drug Rev. 2004 Winter;10(4):317-36.

Aripiprazole is an N-arylpiperazine that is piperazine substituted by a 4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]butyl group at position 1 and by a 2,3-dichlorophenyl group at position 4. It is an antipsychotic drug used for the treatment of Schizophrenia, and other mood disorders. It has a role as a H1-receptor antagonist, a serotonergic agonist, a second generation antipsychotic and a drug metabolite. It is a quinolone, a N-arylpiperazine, a N-alkylpiperazine, a dichlorobenzene, an aromatic ether and a delta-lactam.
Aripiprazole is an atypical antipsychotic orally indicated for the treatment of schizophrenia, bipolar I, major depressive disorder, irritability associated with autism, and Tourette's. It is also indicated as an injection for agitation associated with schizophrenia or bipolar mania. Aripiprazole exerts its effects through agonism of dopaminergic and 5-HT1A receptors and antagonism of alpha-adrenergic and 5-HT2A receptors. Aripiprazole was given FDA approval on November 15, 2002.
Aripiprazole is an Atypical Antipsychotic.
Aripiprazole is an atypical antipsychotic used in the treatment of schizophrenia and bipolar illness. Aripiprazole therapy has not been associated consistently with serum aminotransferase elevations and has yet to be linked to cases of clinically apparent acute liver injury.
Aripiprazole is a quinoline derivate and atypical anti-psychotic agent. Aripiprazole has partial agonistic activity at dopamine D2 receptors and serotonin 5-HT1A receptors, as well as potent antagonistic activity on serotonin 5-HT2A receptors. This drug stabilizes dopamine and serotonin activity in the limbic and cortical system. Aripiprazole is used in managing symptoms of schizophrenia and of acute manic and mixed episodes associated with bipolar I disorders.
Aripiprazole is an atypical antipsychotic medication used for the treatment of schizophrenia. It has also recently received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder. Aripiprazole appears to mediate its antipsychotic effects primarily by partial agonism at the D2 receptor. In addition to partial agonist activity at the D2 receptor, aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics, aripiprazole displays an antagonist profile at the 5-HT2A receptor. Aripiprazole has moderate affinity for histamine and alpha adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors.
A piperazine and quinolone derivative that is used primarily as an antipsychotic agent. It is a partial agonist of SEROTONIN RECEPTOR, 5-HT1A and DOPAMINE D2 RECEPTORS, where it also functions as a post-synaptic antagonist, and an antagonist of SEROTONIN RECEPTOR, 5-HT2A. It is used for the treatment of SCHIZOPHRENIA and BIPOLAR DISORDER, and as an adjunct therapy for the treatment of depression.
See also: Aripiprazole Lauroxil (is active moiety of); Aripiprazole Cavoxil (is active moiety of); Aripiprazole monohydrate (annotation moved to).

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Drug Indication
Aripiprazole is indicated for the treatment of acute manic and mixed episodes associated with bipolar I disorder, irritability associated with autism spectrum disorder, schizophrenia, and Tourette's disorder. It is also used as an adjunctive treatment of major depressive disorder.[L45859 An injectable formulation of aripiprazole is indicated for agitation associated with schizophrenia or bipolar mania. Finally, an extended-release, bimonthly injection formulation of aripiprazole is indicated for the treatment of adult schizophrenia and maintenance therapy for adult bipolar I disorder.
FDA Label
Aripiprazole Mylan Pharma is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older. Aripiprazole Mylan Pharma is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment. Aripiprazole Mylan Pharma is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.
Maintenance treatment of schizophrenia in adult patients stabilised with oral aripiprazole.
Aripiprazole Sandoz is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older. , , Aripiprazole Sandoz is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment. , , Aripiprazole Sandoz is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older. ,
Aripiprazole Zentiva is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older. Aripiprazole Zentiva is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment. Aripiprazole Zentiva is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.
Aripiprazole Accord is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older. , , Aripiprazole Accord is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment. , , Aripiprazole Accord is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older. ,
Abilify is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older. Abilify is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder and for the prevention of a new manic episode in adults who experienced predominantly manic episodes and whose manic episodes responded to aripiprazole treatment. Abilify is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in Bipolar I Disorder in adolescents aged 13 years and older.
Treatment of bipolar affective disorder, Treatment of schizophrenia

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Mechanism of Action
The antipsychotic action of aripiprazole is likely due to its partial agonist activity on D2 and 5-HT_1A receptors as well as its antagonist activity at 5-HT_2A receptors; however, the exact mechanism has not been fully elucidated. One of the mechanisms that have been proposed is that aripiprazole both stimulates and inhibits dopamine as it engages the D2 receptor. It lowers dopamine neuronal firing at high dopamine concentrations and increases dopamine firing at low concentrations. Its partial agonist activity gives aripiprazole an intermediate level of dopaminergic neuronal tone between full agonist and antagonist of the D2 receptor. In addition, some adverse effects may be due to action on other receptors. For example, orthostatic hypotension may be explained by antagonism of the adrenergic alpha-1 receptors.
The exact mechanism of antipsychotic action of aripiprazole has not been fully elucidated but, like that of other atypical antipsychotic agents (e.g.,olanzipine, risperidone, ziprasidon), may involve the drug's activity at dopamine D2 and serotonin type (5-HT1A) and type 2 (5-HT2A) receptors. However, aripiprazole appears to differ from other atypical antipsychotic agents because the drug demonstrates partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Antagonism at other receptors (e.g., alpha1-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence) observed with aripiprazole.
...Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the mesolimbic pathway, as well as having unique partial agonist activity at D2 receptors in the mesocortical pathway. As exemplified by other atypical antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. ...Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles ...

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Atypical antipsychotic drugs have revolutionized the treatment of schizophrenia and related disorders. The current clinically approved atypical antipsychotic drugs are characterized by having relatively low affinities for D(2)-dopamine receptors and relatively high affinities for 5-HT(2A) serotonin receptors (5-HT, 5-hydroxytryptamine (serotonin)). Aripiprazole (OPC-14597) is a novel atypical antipsychotic drug that is reported to be a high-affinity D(2)-dopamine receptor partial agonist. We now provide a comprehensive pharmacological profile of aripiprazole at a large number of cloned G protein-coupled receptors, transporters, and ion channels. These data reveal a number of interesting and potentially important molecular targets for which aripiprazole has affinity. Aripiprazole has highest affinity for h5-HT(2B)-, hD(2L)-, and hD(3)-dopamine receptors, but also has significant affinity (5-30 nM) for several other 5-HT receptors (5-HT(1A), 5-HT(2A), 5-HT(7)), as well as alpha(1A)-adrenergic and hH(1)-histamine receptors. Aripiprazole has less affinity (30-200 nM) for other G protein-coupled receptors, including the 5-HT(1D), 5-HT(2C), alpha(1B)-, alpha(2A)-, alpha(2B)-, alpha(2C)-, beta(1)-, and beta(2)-adrenergic, and H(3)-histamine receptors. Functionally, aripiprazole is an inverse agonist at 5-HT(2B) receptors and displays partial agonist actions at 5-HT(2A), 5-HT(2C), D(3), and D(4) receptors. Interestingly, we also discovered that the functional actions of aripiprazole at cloned human D(2)-dopamine receptors are cell-type selective, and that a range of actions (eg agonism, partial agonism, antagonism) at cloned D(2)-dopamine receptors are possible depending upon the cell type and function examined. This mixture of functional actions at D(2)-dopamine receptors is consistent with the hypothesis proposed by Lawler et al (1999) that aripiprazole has "functionally selective" actions. Taken together, our results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of "functionally selective" activation of D(2) (and possibly D(3))-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors--particularly 5-HT receptor subtypes (5-HT(1A), 5-HT(2A)).[2]

C23H29CL2N3O3

466.4007

465.159

C, 59.23; H, 6.27; Cl, 15.20; N, 9.01; O, 10.29

851220-85-4

Aripiprazole; 129722-12-9; Aripiprazole-d8; 1089115-06-9; 851220-85-4 (hydrate); 1259305-26-4 (cavoxil); 1259305-29-7 (lauroxil)

11408688

Solid powder

4.883

57.53

2

5

7

31

559

0

ClC1C(=C([H])C([H])=C([H])C=1N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])C([H])([H])OC2C([H])=C([H])C3=C(C=2[H])N([H])C(C([H])([H])C3([H])[H])=O)C([H])([H])C1([H])[H])Cl.O([H])[H]

UXQBDXJXIVDBTF-UHFFFAOYSA-N

InChI=1S/C23H27Cl2N3O2.H2O/c24-19-4-3-5-21(23(19)25)28-13-11-27(12-14-28)10-1-2-15-30-18-8-6-17-7-9-22(29)26-20(17)16-18;/h3-6,8,16H,1-2,7,9-15H2,(H,26,29);1H2

7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-quinolin-2-one;hydrate

OPC 31; OPC14597; OPC-31; OPC 14597; Aripiprazole monohydrate; Aripiprazole hydrate; 851220-85-4; UNII-O362MEQ7VR; O362MEQ7VR; Aripiprazole (monohydrate); Aripiprazole hydrate (JAN); ARIPIPRAZOLE HYDRATE [JAN]; OPC31; Abilitat; OPC-14597

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。