Tonabersat
(Synonyms: SB-220453;SB 220453;SB220453) 目录号 : GC16494
An anti-migraine agent
Cas No.:175013-84-0
Sample solution is provided at 25 µL, 10mM.
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Migraine is a common, recurrent and primary headache disorder. Optimisation of novel cis- and trans-4-(substituted-anfido)benzopyran-3-ol derivatives has led to the identification of Tonabersat (SB-220453) with potential antimigraine activity.
In vitro: Topiramate targets multiple cortical and subcortical loci, altering voltage-gated ion channels and chemical transmission to decrease abnormal brain excitability. Preclinical studies have identified four properties that may account for the drug’s efficacy in epilepsy and migraine prophylaxis: (i) blockage of voltage-dependent sodium channels; (ii) augmentation of the activity of the neurotransmitter g-aminobutyric acid (GABA) at some subtypes of the GABA-A receptor; (iii) antagonism of the AMPA/kainate subtype of the glutamate receptor; and (iv) inhibition of the carbonic anhydrase enzymes, particularly isozymes II and IV [1].
In vivo: Tonabersat binds selectively to a unique site in the brain. Moreover, tonabersat could markedly reduce cortical spreading depression (CSD) and CSD-associated events and inhibite gap-junction communication between neurons and satellite glial cells in the trigeminal ganglion. Together, these findings indicate that tonabersat should have clinical application in preventing migraine attacks [2].
Clinical trial: Tonabersat showed a preventive eff ect on attacks of migraine aura but no efficacy on non-aura attacks, in keeping with its known inhibitory eff ect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura [3].
References:
[1] Silberstein SD. Tonabersat, a novel gap-junction modulator for the prevention of migraine. Cephalalgia. 2009;29 Suppl 2:28-35.
[2] Durham PL, Garrett FG. Neurological mechanisms of migraine: potential of the gap-junction modulator tonabersat in prevention of migraine. Cephalalgia. 2009;29 Suppl 2:1-6.
[3] Hauge AW, Asghar MS, Schytz HW, Christensen K, Olesen J. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. Lancet Neurol. 2009;8(8):718-23.
Animal experiment: | Mice[2] Athymic NCR nu/nu mice, Cr:NIH bg-nu-xid mice, B6129SF1/J, C57BL/6J-Tmem173gt/J 'golden ticket', and C57/Bl/6J mice are used at 5-6 weeks of age. For inducible knockdown experiments, mice are given doxycycline hyclate in the drinking water (2 mg/mL) and the diet 14 days after injection of cancer cells. For drug treatment experiments, mice are intraperitoneally injected with Carboplatin (5 mg/kg per 5 days), Tonabersat (MedChem Express) (10 mg/kg per day), or meclofenamic acid sodium salt (20 mg/kg per day). Vehicle (10% DMSO in polyethylene glycol 400) is used in control mice. Quantification of tumour burden is by Bio-luminescent imaging (BLI), performed using an IVIS Spectrum Xenogen instrument and analysed using Living Image software v.2.50. |
References: [1]. Silberstein SD, et al. Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine. Cephalalgia. 2009 Nov;29 Suppl 2:17-27. | |
| Cas No. | 175013-84-0 | SDF | |
| 别名 | SB-220453;SB 220453;SB220453 | ||
| 化学名 | N-[(3S,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-3-chloro-4-fluorobenzamide | ||
| Canonical SMILES | CC(=O)C1=CC2=C(C=C1)OC(C(C2NC(=O)C3=CC(=C(C=C3)F)Cl)O)(C)C | ||
| 分子式 | C20H19ClFNO4 | 分子量 | 391.82 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2)(1:9): 0.1 mg/ml,Ethanol: 20 mg/ml | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5522 mL | 12.761 mL | 25.5219 mL |
| 5 mM | 0.5104 mL | 2.5522 mL | 5.1044 mL |
| 10 mM | 0.2552 mL | 1.2761 mL | 2.5522 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。
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet