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Retigabine dihydrochloride

现货
Catalog No.
A3758
K+通道(KCNQ)开放剂,抗癫痫化合物
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
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5mg
¥ 465.00
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10mg
¥ 744.00
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50mg
¥ 1,906.00
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100mg
¥ 3,329.00
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Background

IC50: N/A

Retigabine is a first-in-class K+ channel (KCNQ) opener. KCNQ channels are reported to be expressed predominantly in neurons and are critical determinants of cellular excitability, as shown by the occurrence of human genetic mutations in KCNQ channels which underlie inheritable disorders including the syndrome of benign familial neonatal convulsions.

In vitro: Retigabine was found to combine a novel mode of actions, which were namely potassium channel opening (KCNQ2, KCNQ3 as well as KCNQ4 channels). Retigabine also showed activities with some potentiation of gamma amino butyric acid (GABA)-evoked currents at its higher concentrations [1].

In vivo: Animal models of epileptic seizures showed that retigabine treatment was effective at an oral dose as low as 0.01 mg/kg. Studies performed in mice also indicated that combining retigabine with another anticonvulsant agent leads to an additive effect [1].

Clinical trial: A clinical interaction study showed that there was no pharmacokinetic interaction between phenobarbitone and retigabine in healthy subjects. Thus, no dosage adjustment is likely to be necessary when phenobarbitone and retigabine are coadministered to patients [1].

Reference:
[1] Ferron GM,Patat A,Parks V,Rolan P,Troy SM.  Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. Br J Clin Pharmacol.2003 Jul;56(1):39-45.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt376.25
Cas No.150812-13-8
FormulaC16H20Cl2FN3O2
SynonymsD 20443 dihydrochloride;D-20443 dihydrochloride;D20443 dihydrochloride
Solubility≥18.8 mg/mL in DMSO, ≥8.71 mg/mL in EtOH with ultrasonic and warming, ≥52.4 mg/mL in H2O with gentle warming
Chemical Nameethyl N-[2-amino-4-[(4-fluorophenyl)methylamino]phenyl]carbamate;dihydrochloride
SDFDownload SDF
Canonical SMILESCCOC(=O)NC1=C(C=C(C=C1)NCC2=CC=C(C=C2)F)N.Cl.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

转染KCNQ2/Q3串联结构的中国仓鼠卵巢 (CHO-K1) 细胞 (CHO-KCNQ2/Q3)

制备方法

可溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

0.1 ~ 10 μM

实验结果

Retigabine Dihydrochloride (0.1 ~ 10 μM) 刺激钾电流。此外,Retigabine Dihydrochloride使CHO-KCNQ2/Q3细胞超极化,而对野生型细胞无影响。

动物实验 [2]:

动物模型

小鼠6-Hz精神运动癫痫发作模型

给药剂量

26或33 mg/kg;腹腔注射

实验结果

在6-Hz精神运动癫痫模型中,Retigabine Dihydrochloride呈剂量依赖性地阻断32或44 mA电流刺激诱发的癫痫发作。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600.

[2]. Large CH, Sokal DM, Nehlig A, Gunthorpe MJ, Sankar R, Crean CS, Vanlandingham KE, White HS. The spectrum of anticonvulsant efficacy of retigabine (ezogabine) in animal models: implications for clinical use. Epilepsia. 2012 Mar;53(3):425-36.

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