Tetrabenazine
(Synonyms: (+)-丁苯那嗪; (+)-TBZ; (3R,11bR)-TBZ; (3R,11bR)-Tetrabenazine) 目录号 : GC13672
丁苯那嗪是美国食品和药物管理局唯一批准的亨廷顿舞蹈病药物，适用于治疗与亨廷顿舞蹈病相关的舞蹈症。
Cas No.:58-46-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Tetrabenazine is the only US Food and Drug Administration-approved drug for Huntington's disease, indicated for treatment of chorea associated with Huntington's disease[1,3,4]. It reversibly inhibits central vesicular monoamine transporter (VMAT) transporter type 2 which acts on the various monoaminergic systems in the brain, e.g., dopamine, serotonin and noradrenaline[5] Tetrabenazine binds predominately to VMAT2 and has been shown to reversibly inhibit monoamine uptake in pre-synaptic vesicles, resulting in monoamine depletion of serotonin, dopamine, and nor-epinephrine [6] thereby reducing chorea[7].
In Neuro-2a neuroblastoma cell line, Tetrabenazine loaded nanoemulsion showed 100.00±1.23%, 100.00±2.01% and 100.00±2.09% cell viability when treated at the dose of 4.8ng/mL, 2.4ng/mL and 9.6ng/Ml[2]. When used bovine chromaffin cells (BCCs) challenged with repeated pulses of high K+ Upon repeated K+ pulsing, the exocytotic catecholamine release responses were gradually decaying. However, when cells were exposed to tetrabenazine, responses were mildly augmented and decay rate delayed[8].
In rat, The superiority of tetrabenazine nanoemulsion for delivering of tetrabenazine via intranasal route bypassing BBB[2]. In mice, Cold-water immersion-induced acute stress diminished the locomotor activity, exploratory behaviour, motor activity and social behaviour along with increase in the plasma corticosterone levels. Administration of tetrabenazine (1 and 2 mg/kg, i.p.), abolished the acute stress-induced behavioural and biochemical changes in a dose-dependent manner[9].
References:
[1]. Peter D, Vu T, et,al.Chimeric vesicular monoamine transporters identify structural domains that influence substrate affinity and sensitivity to tetrabenazine. J Biol Chem. 1996 Feb 9;271(6):2979-86. doi: 10.1074/jbc.271.6.2979. PMID: 8621690.
[2]. Arora A, Kumar S, et,al. Intranasal delivery of tetrabenazine nanoemulsion via olfactory region for better treatment of hyperkinetic movement associated with Huntington's disease: Pharmacokinetic and brain delivery study. Chem Phys Lipids. 2020 Aug;230:104917. doi: 10.1016/j.chemphyslip.2020.104917. Epub 2020 May 19. PMID: 32439327.
[3]. Kenney C, Hunter C, et,al. Short-term effects of tetrabenazine on chorea associated with Huntington's disease. Mov Disord. 2007 Jan;22(1):10-3. doi: 10.1002/mds.21161. PMID: 17078062.
[4]. Mestre TA, Ferreira JJ. An evidence-based approach in the treatment of Huntington's disease. Parkinsonism Relat Disord. 2012 May;18(4):316-20. doi: 10.1016/j.parkreldis.2011.10.021. Epub 2011 Dec 16. PMID: 22177624.
[5]. Thibaut F, Faucheux BA, et,al. Regional distribution of monoamine vesicular uptake sites in the mesencephalon of control subjects and patients with Parkinson's disease: a postmortem study using tritiated tetrabenazine. Brain Res. 1995 Sep 18;692(1-2):233-43. doi: 10.1016/0006-8993(95)00674-f. PMID: 8548309.
[6]. Pettibone DJ, Totaro JA, et,al. Tetrabenazine-induced depletion of brain monoamines: characterization and interaction with selected antidepressants. Eur J Pharmacol. 1984 Jul 20;102(3-4):425-30. doi: 10.1016/0014-2999(84)90562-4. PMID: 6489435.
[7]. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006 Feb 14;66(3):366-72. doi: 10.1212/01.wnl.0000198586.85250.13. PMID: 16476934.
[8]. de Pascual R, álvarez-Ortego N,et,al. Tetrabenazine Facilitates Exocytosis by Enhancing Calcium-Induced Calcium Release through Ryanodine Receptors. J Pharmacol Exp Ther. 2019 Oct;371(1):219-230. doi: 10.1124/jpet.119.256560. Epub 2019 Jun 17. PMID: 31209099.
[9].Kumar M, Singh N, et,al. Exploring the anti-stress effects of imatinib and tetrabenazine in cold-water immersion-induced acute stress in mice. Naunyn Schmiedebergs Arch Pharmacol. 2020 Sep;393(9):1625-1634. doi: 10.1007/s00210-020-01862-w. Epub 2020 Apr 14. PMID: 32291496.
丁苯那嗪是美国食品和药物管理局唯一批准的亨廷顿舞蹈病药物,适用于治疗与亨廷顿舞蹈病相关的舞蹈症[1,3,4]。它可逆地抑制 2 型中央囊泡单胺转运蛋白 (VMAT) 转运蛋白,后者作用于大脑中的各种单胺能系统,例如多巴胺、5-羟色胺和去甲肾上腺素[5] Tetrabenazine 主要与 VMAT2 结合并已被证明可逆地抑制突触前小泡中的单胺摄取,导致血清素、多巴胺和去甲肾上腺素的单胺消耗[6],从而减少舞蹈病[7]。\n
在 Neuro-2a 神经母细胞瘤细胞系中,负载 Tetrabenazine 的纳米乳剂以 4.8ng/mL、2.4ng/mL 和 9.6ng/mL 的剂量处理时显示出 100.00±1.23%、100.00±2.01% 和 100.00±2.09% 的细胞活力毫升[2]。当使用重复的高 K+ 脉冲攻击牛嗜铬细胞 (BCC) 时 在重复 K+ 脉冲下,胞吐儿茶酚胺释放反应逐渐衰减。然而,当细胞暴露于丁苯那嗪时,反应会轻度增强,衰减速率会延迟[8]。
在大鼠中,丁苯那嗪纳米乳剂通过鼻内途径绕过 BBB 递送丁苯那嗪的优势[2]。在小鼠中,冷水浸泡引起的急性应激会降低运动活动、探索行为、运动活动和社交行为,同时血浆皮质酮水平也会升高。施用丁苯那嗪（1 和 2 mg/kg,腹腔注射）,以剂量依赖性方式消除急性应激诱导的行为和生化变化[9]。
| Cell experiment [1]: | |
|
Cell lines |
Neuro-2a neuroblastoma cell line |
|
Preparation Method |
Neuro-2a cells were incubated for 24h with tetrabenazine solution, tetrabenazine loaded nanoemulsion and placebo. |
|
Reaction Conditions |
2.4/4.8/9.6 ng/mL Tetrabenazine for 24h |
|
Applications |
Tetrabenazine loaded nanoemulsion showed 100.00±1.23%, 100.00±2.01% and 100.00±2.09% cell viability when treated at the dose of 4.8ng/mL, 2.4ng/mL and 9.6ng/Ml. |
| Animal experiment [2]: | |
|
Animal models |
Wistar rats (200-250g) of age 11-12 weeks |
|
Preparation Method |
Tetrabenazine solution was administered intravenously to group 1 (dose 1.25mg/day dissolved in 1mL of normal saline solution). Second group of animals received tetrabenazine nanoemulsion administered intranasally (dose equivalent to 1.25mg/day). Dosage volume administered to each nostril was 25µL. Rats were sacrificed humanely by cervical dislocation method at different time intervals (0.5, 1, 6 and 12h) after collecting blood from retino-orbital vein in precoated EDTA tube. |
|
Dosage form |
Group 1：1.25mg/day Tetrabenazine in 1mL saline; iv |
|
Applications |
The superiority of tetrabenazine nanoemulsion for delivering of tetrabenazine via intranasal route bypassing BBB. |
|
References: [1].Arora A, Kumar S, Ali J, Baboota S. Intranasal delivery of tetrabenazine nanoemulsion via olfactory region for better treatment of hyperkinetic movement associated with Huntington's disease: Pharmacokinetic and brain delivery study. Chem Phys Lipids. 2020 Aug;230:104917. doi: 10.1016/j.chemphyslip.2020.104917. Epub 2020 May 19. PMID: 32439327. |
|
| Cas No. | 58-46-8 | SDF | |
| 别名 | (+)-丁苯那嗪; (+)-TBZ; (3R,11bR)-TBZ; (3R,11bR)-Tetrabenazine | ||
| 化学名 | 3-isobutyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one | ||
| Canonical SMILES | CC(CC1CN2CCC3=CC(OC)=C(OC)C=C3C2CC1=O)C | ||
| 分子式 | C19H27NO3 | 分子量 | 317.42 |
| 溶解度 | ≥ 9mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.1504 mL | 15.752 mL | 31.504 mL |
| 5 mM | 0.6301 mL | 3.1504 mL | 6.3008 mL |
| 10 mM | 0.315 mL | 1.5752 mL | 3.1504 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet