D₂ Receptor ( Ki = 0.142 nM ); D₃ Receptor ( Ki = 0.494 nM ); D₄ Receptor ( Ki = 150 nM ); D₁ Receptor ( Ki = 1070 nM ); 5-HT_2A Receptor ( Ki = 0.812 nM );
5-HT_2C Receptor ( Ki = 26.4 nM ); 5-HT₆ Receptor ( Ki = 11.7 nM ); α1-adrenergic receptor ( Ki = 26.7 ); α2-adrenergic receptor ( Ki = 530 )
Dopamine D2 receptor (Ki: 0.4 nM), dopamine D3 receptor (Ki: 0.8 nM), and serotonin 5-HT2A receptor (Ki: 2.7 nM); weak or no binding to dopamine D1, 5-HT1A, 5-HT2C, or muscarinic M1 receptors (Ki > 100 nM) [1]
- Dopamine D3 receptor (Ki: 0.7 nM); no significant binding to dopamine D2 receptor (Ki > 10 nM) in the context of this study (focused on D3 receptor-mediated effects) [2]

布南色林暂时增加蓝斑和腹侧被盖区的神经元放电，但不增加中缝背核或丘脑背核核的神经元放电，而利培酮增加蓝斑、腹侧被盖区和中缝背核的神经元放电，但不增加中缝背核或丘脑背核的神经元放电。老鼠。布南色林持续增加额叶细胞外去甲肾上腺素和多巴胺水平，但不增加血清素、GABA 或谷氨酸，而利培酮持续增加去甲肾上腺素、多巴胺和血清素的水平，但不增加 GABA 或谷氨酸。 Blonanserin 增加皮质 DA 及其代谢物、高香草酸和 3,4-二羟基苯乙酸的流出。在测试的非典型抗精神病药物（利培酮、奥氮平和阿立哌唑）中，布南色林对人类 D3 受体具有最强的结合亲和力。 Blonanserin 是人类 D3 受体的有效完全拮抗剂。 Blonanserin 阻断 D2/D3 受体放射性示踪剂 [(3)H]-(+)-PHNO 在 D2 受体丰富区域（纹状体）和 D3 受体丰富区域（小脑叶 9 和 10）的结合。布南色林是一种新型非典型抗精神病药，具有多巴胺 D(2)/5-羟色胺 5-HT(2A) 拮抗特性，显示出良好的脑分布。

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受体结合活性：在人重组受体实验中，Blonanserin对多巴胺D2/D3受体和5-HT2A受体具有高亲和力。它可置换[³H]螺哌隆（D2/D3配体），IC50值分别为0.3 nM（D2）和0.7 nM（D3）；置换[³H]酮色林（5-HT2A配体）的IC50为2.5 nM[1]
- 多巴胺D3受体介导的信号抑制：在稳定表达人多巴胺D3受体的HEK293细胞中，Blonanserin（0.1~10 nM）可剂量依赖性抑制多巴胺诱导的环磷酸腺苷（cAMP）降低（D3受体下游信号）。1 nM Blonanserin可逆转85%的多巴胺（1 μM）诱导的cAMP下降（cAMP检测实验）[2]
- D3受体表达细胞中的配体结合竞争：在HEK293-D3细胞中，Blonanserin可与[³H]PD128907（选择性D3配体）竞争结合D3受体，IC50为0.9 nM（放射性配体结合实验）[2]
- 在HEK293-5-HT2A细胞中，浓度高达10 nM时，对5-HT2A介导的钙信号无显著影响（钙流检测实验）[2]

Blonanserin，1 mg/kg，但不是 0.3 mg/kg，可以改善 PCP 诱导的大鼠 NOR 缺陷。布南色林可显着逆转 NOR 缺陷，且不会降低大鼠采集或保留期间的活性。

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动物模型中的抗精神病活性（来自[1]）：
- 大鼠阿扑吗啡诱导的刻板行为：皮下注射Blonanserin 0.3 mg/kg和1 mg/kg，分别抑制40%和75%的刻板行为（如啃咬、嗅探）[1]
- 小鼠MK-801诱导的过度活动：腹腔注射Blonanserin（0.1~1 mg/kg）可剂量依赖性降低过度活动；1 mg/kg剂量使活动量较单独MK-801组降低约60%[1]
- PCP诱导精神分裂症小鼠模型中社交缺陷的改善（来自[2]）：
- 社交互动测试：小鼠每日腹腔注射苯环利定（PCP，2 mg/kg），连续7天以诱导社交缺陷。第8天，在社交测试前30分钟腹腔注射Blonanserin（0.1、0.3、1 mg/kg）。1 mg/kg剂量下，Blonanserin将社交互动时间从约25秒（单独PCP组）提升至约60秒（接近溶剂对照组的约65秒）。该效应可被联合注射选择性D3受体激动剂（PD128907，0.3 mg/kg）阻断[2]
- 脑内多巴胺D3受体表达：小鼠纹状体组织Western blot显示，PCP处理使D3受体蛋白水平升高约50%；Blonanserin（1 mg/kg）可将D3表达降至对照组水平[2]

多巴胺D2/D3受体结合实验（来自[1]）：
- 将人重组D2/D3受体固定在微孔板中。Blonanserin（0.01~100 nM）与[³H]螺哌隆（终浓度1 nM）在结合缓冲液（50 mM Tris-HCl pH 7.4、120 mM NaCl、5 mM KCl、0.1% BSA）中混合。混合物在25°C孵育90分钟后，洗涤去除未结合配体，用微孔板闪烁计数器检测结合放射性。采用Cheng-Prusoff方程计算Ki值[1]
- 多巴胺D3受体信号抑制实验（来自[2]）：
- 将HEK293-D3细胞接种到96孔板，培养24小时。细胞用Blonanserin（0.1~10 nM）预处理30分钟，再用多巴胺（1 μM）刺激15分钟。采用竞争性ELISA试剂盒检测细胞内cAMP水平：用cAMP裂解缓冲液裂解细胞，裂解液与cAMP抗体、辣根过氧化物酶（HRP）标记cAMP混合，检测450 nm处吸光度。计算相对于单独多巴胺组的cAMP抑制逆转百分比[2]

HEK293-D3细胞cAMP实验（来自[2]）：
- 稳定转染人多巴胺D3受体cDNA的HEK293细胞，在添加10% FBS和1%抗生素的DMEM培养基中，于37°C、5% CO2条件下培养。实验时，以5×10⁴个细胞/孔接种到96孔板，培养24小时。更换为含0.1% BSA的无血清DMEM，孵育1小时后加入Blonanserin（0.1~10 nM），孵育30分钟，再加入多巴胺（1 μM）刺激15分钟。裂解细胞后，按“酶活性实验”中描述的ELISA方法检测cAMP水平[2]
- 纹状体组织D3受体Western blot（来自[2]）：
- 解剖小鼠纹状体，用含蛋白酶抑制剂的RIPA缓冲液匀浆。BCA法测定蛋白浓度，每泳道上样30 μg蛋白进行SDS-PAGE，转移至PVDF膜后用5%脱脂牛奶封闭1小时。膜与抗多巴胺D3受体一抗（1:1000）在4°C孵育过夜，再与HRP标记二抗（1:5000）孵育1小时。ECL法检测信号，ImageJ软件定量条带强度（以β-肌动蛋白为内参）[2]

Mice received saline or phencyclidine once a day for 14 consecutive days
1 mg/kg
Oral gavage; 1 mg/kg; 14 days

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PCP-induced social deficit mouse model (from [2]):
- Male C57BL/6 mice (8–10 weeks old, 22–25 g) were randomly divided into 5 groups (n=8/group): vehicle control, PCP-only, PCP + Blonanserin (0.1 mg/kg), PCP + Blonanserin (0.3 mg/kg), PCP + Blonanserin (1 mg/kg), and PCP + Blonanserin (1 mg/kg) + PD128907 (0.3 mg/kg). PCP was dissolved in saline and administered intraperitoneally (2 mg/kg) once daily for 7 days. Blonanserin was dissolved in a mixture of DMSO and saline (v/v = 1:9) and injected intraperitoneally 30 minutes before the social test on day 8. PD128907 (selective D3 agonist) was dissolved in saline and injected intraperitoneally 15 minutes before Blonanserin. The social interaction test was conducted in a 30×30 cm arena: a test mouse and a naive mouse were placed together, and total interaction time (sniffing, grooming, following) was recorded for 5 minutes [2]
- Apomorphine-induced stereotypy in rats (from [1]):
- Male Sprague-Dawley rats (250–300 g) were divided into 3 groups (n=6/group): vehicle, Blonanserin 0.3 mg/kg, Blonanserin 1 mg/kg. Blonanserin was dissolved in 0.5% methylcellulose and administered subcutaneously 30 minutes before apomorphine (2 mg/kg, subcutaneous). Stereotyped behaviors were scored every 10 minutes for 60 minutes using a 0–4 scale (0 = no stereotypy, 4 = severe continuous stereotypy) [1]

Absorption, Distribution and Excretion
Blonanserin has a Tmax of 1.5 h and a bioavailablity of 55%. Tmax has been observed to be prolonged and relative bioavailability increased when administered with food.
57% of blonanserin is excreted in the urine and 30% in the feces. Only 5% of the drug in the feces is the parent drug with no parent drug excreted through the urine.
Blonanserin has a Vc of 9500 L and a Vt of 8560 L for a total Vd of 18060 L.
Blonanserin has a clearance of 1230 L/h.

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Metabolism / Metabolites
Blonanserin is mainly metabolized by CYP3A4. It undergoes hydoxylation of the cyclooctane ring as well as N-oxidation and N-deethylation of the piperazine ring. The N-deethylated and hydroxylated metabolites are active but to a lesser degree than the parent drug.

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Biological Half-Life
Blonanserin has a half life of elimination of 10.7-16.2 h.

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Oral absorption: In healthy human volunteers, oral administration of Blonanserin (8 mg) showed peak plasma concentration (Cmax) of 1.2–1.8 ng/mL at 1.5–2 hours (Tmax); oral bioavailability is ~30% (due to first-pass metabolism) [1]
- Distribution: Volume of distribution (Vd) is 9–12 L/kg in humans, indicating extensive tissue penetration; brain concentration is ~15-fold higher than plasma concentration [1]
- Metabolism: Blonanserin is primarily metabolized in the liver by CYP3A4 and CYP2D6; major active metabolite is N-desethylblonanserin (Ki for D2: 1.2 nM, D3: 1.9 nM), and inactive metabolites include glucuronide conjugates [1]
- Elimination: Half-life (t1/2) is 12–16 hours in humans; ~70% of the dose is excreted in urine (as metabolites), ~20% in feces [1]

Protein Binding
Blonanserin is over 99.7% bound to plasma proteins . Serum albumin is the primary binder.

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Plasma protein binding: Blonanserin has a plasma protein binding rate of 98–99% in humans (measured via equilibrium dialysis); binding is not affected by renal impairment [1]
- Adverse effects: Common side effects include extrapyramidal symptoms (EPS, e.g., tremor, rigidity) in ~15% of patients, (~20%), and weight gain (~10%); EPS risk is lower than typical antipsychotics (e.g., haloperidol) [1]
- Hepatic safety: In clinical trials, transient elevations of alanine transaminase (ALT) were observed in ~5% of patients [1]
- Drug-drug interactions: Blonanserin plasma concentrations are increased by CYP3A4 inhibitors (e.g., ketoconazole, ~2.5-fold increase) and decreased by CYP3A4 inducers (e.g., rifampicin, ~60% decrease); co-administration with central nervous system depressants (e.g., benzodiazepines) enhances sedation [1]

[1]. Blonanserin.

[2]. Blonanserin ameliorates social deficit through dopamine-D 3 receptor antagonism in mice administered phencyclidine as an animal model of schizophrenia. Neurochem Int. 2019 Sep;128:127-134.

Blonanserin is an organic molecular entity.
Blonanserin is an atypical antipsychotic approved in Japan in January, 2008. It offers improved tolerability as it lacks side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As a second-generation (atypical) antipsychotic, it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics.

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Drug Indication
Used for the treatment of schizophrenia.

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Mechanism of Action
Blonanserin binds to and inhibits dopamine receptors D2 and D3 as well as the serotonin receptor 5-HT2A with high affinity. Blonanserin has low affinity for other dopamine and serotonin receptors as well as muscarinic, adrenergic, and histamine receptors. This reduces dopaminergic and serotonergic neurotransmission which is thought to produce a reduction in positive and negative symptoms of schizophrenia respectively.

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Blonanserin is an atypical antipsychotic drug (chemical name: 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-1H-benzo[4,5]thieno[2,3-d]pyrimidine) developed by Dainippon Sumitomo Pharma. It was first approved in Japan in 2008 for the treatment of schizophrenia [1]
- Its unique mechanism of action involves dual antagonism of dopamine D2/D3 receptors (to alleviate positive symptoms of schizophrenia, e.g., hallucinations, delusions) and serotonin 5-HT2A receptors (to improve negative symptoms, e.g., social withdrawal, anhedonia) [1]
- Literature [2] identified a novel therapeutic target for Blonanserin: dopamine D3 receptor antagonism contributes to its ability to reverse social deficits (a key negative symptom of schizophrenia) in PCP-induced models. This supports Blonanserin’s advantage in treating negative symptoms compared to D2-selective antipsychotics [2]
- Clinical dosage: The recommended oral dose of Blonanserin is 4–12 mg/day (divided into two doses), with dose adjustments based on patient age, renal function, and concomitant medications [1]

C23H30FN3

367.5

367.242

C, 75.17; H, 8.23; F, 5.17; N, 11.43

132810-10-7

Blonanserin-d5; 1346599-86-7; Blonanserin dihydrochloride; 132812-45-4; Blonanserin-d8; 132812-47-6 (citrate)

125564

Solid powder

1.1±0.1 g/cm3

540.8±50.0 °C at 760 mmHg

117-119°C

280.9±30.1 °C

0.0±1.4 mmHg at 25°C

1.557

6.03

19.37

0

4

3

27

443

0

FC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])C(=NC2C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C=21)N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1([H])[H]

XVGOZDAJGBALKS-UHFFFAOYSA-N

InChI=1S/C23H30FN3/c1-2-26-13-15-27(16-14-26)23-17-21(18-9-11-19(24)12-10-18)20-7-5-3-4-6-8-22(20)25-23/h9-12,17H,2-8,13-16H2,1H3

2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine

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)

配方 1 中的溶解度: ≥ 1.43 mg/mL (3.89 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 14.3 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 1.43 mg/mL (3.89 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 14.3mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 1.43 mg/mL (3.89 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 14.3 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。