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Topiramate

现货
Catalog No.
A4360
GluR5 受体的拮抗剂,抗惊厥剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
现货
100mg
¥ 740.00
现货

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Background

Topiramate, a novel anticonvulsant drug, is a widely used antiepileptic agent. The drug has been reported to interact with various ion channel types, such as AMPA/kainate receptors, voltage-sensitive Na+ channels, NMDA receptors and GABA receptors [1,2].

In vitro:In principal neurons of the rat basolateral amygdala, low concentrations of topiramate selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors with the GluR5 subunit with an IC50 value of 0.5 μM. Topiramate also partially depressed predominantly AMPA-receptor-mediated EPSCs with lower efficacy [1]. In dissociated neocortical slices, low concentrations of TPM (25–30 μM) slightly inhibited the persistent fraction of Na+ current and reduced the Na+-dependent long-lasting action potential shoulders evoked in layer V pyramidal neurons after Ca2+ and K+ current blockade. TPM (100 μM) had no effects on the voltage dependence of activation but induced a leftward shift of the steady-state INaf inactivation curve [3].

In vivo: TPM treatment significantly improved the 24-h neurological deficit scores (high dose, 1.17 ± 0.41; low dose, 1.75 ± 0.5; p < 0.05 for both doses). The percentage of infarct volume (low dose, 22.9 ± 8.9%, p = 0.002; high dose 7.6 ± 3.4%, p < 0.001) reduced when compared with the controls (infarct size, 54.2 ± 9.0%; neurobehavior score, 2. 67 ± 0.52). Higher dose of TPM induced more neuroprotection than that of lower dose (p < 0.05). In a rat model of focal ischemia, treatment with TPM 2 h after MCA embolization resulted in neuroprotective effect in a dose- and use-dependent manner [2]. Topiramate (25-100 mg/kg, i.p.) dose-dependently elevated the threshold for clonic seizures induced by infusion of a selective agonist of GluR5 kainate receptors ATPA [4]. Topiramate (i.p) effectively suppressed acute seizures induced by perinatal hypoxia in a dose-dependent manner with an ED50 of 2.1 mg/kg [5]. Topiramate (20 and 40 mg/kg i.p.) dose-dependently inhibited both tonic and absence-like seizures. In DBA/2 mice, topiramate inhibited sound-induced seizures with ED50 of 8.6 mg/kg (p.o) [6].

References:
[1] Gryder D S, Rogawski M A.  Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons[J]. The Journal of neuroscience, 2003, 23(18): 7069-7074.
[2] Yang Y, Shuaib A, Li Q, et al.  Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization[J]. Brain research, 1998, 804(2): 169-176.
[3] Taverna S, Sancini G, Mantegazza M, et al.  Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate[J]. Journal of Pharmacology and Experimental Therapeutics, 1999, 288(3): 960-968.
[4] Kaminski R M, Banerjee M, Rogawski M A.  Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist[J]. Neuropharmacology, 2004, 46(8): 1097-1104.
[5] Koh S, Jensen F E.  Topiramate blocks perinatal hypoxia‐induced seizures in rat pups[J]. Annals of neurology, 2001, 50(3): 366-372.
[6] Nakamura J, Tamura S, Kanda T, et al.  Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice[J]. European journal of pharmacology, 1994, 254(1-2): 83-89.

Chemical Properties

StorageStore at -20°C
M.Wt339.36
Cas No.97240-79-4
FormulaC12H21NO8S
Solubility≥16.95 mg/mL in DMSO, ≥24.1 mg/mL in EtOH, ≥2.22 mg/mL in H2O with ultrasonic
Chemical Name[(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydrodi[1,3]dioxolo[4,5-a:5',3'-d]pyran-3a-yl]methyl sulfamate
SDFDownload SDF
Canonical SMILESCC1(OC2COC3(C(C2O1)OC(O3)(C)C)COS(=O)(=O)N)C
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

神经元

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

25 ~ 400 μM

实验结果

在分离的神经元中,Topiramate呈剂量依赖性地抑制持续性钠电流。

动物实验 [2]:

动物模型

雄性NIH瑞士小鼠

给药剂量

25 ~ 100 mg/kg;腹腔注射

实验结果

在雄性NIH瑞士小鼠,静脉滴注TPA(GluR5红藻氨酸受体选择性激动剂)诱导阵挛性发作。Topiramate(5 ~ 100 mg/kg,腹腔注射)呈剂量依赖性地增加阵挛性发作的阈值。

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]. Taverna S, Sancini G, Mantegazza M, Franceschetti S, Avanzini G. Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate. J Pharmacol Exp Ther. 1999 Mar;288(3):960-8.

[2]. Kaminski RM, Banerjee M, Rogawski MA. Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology. 2004 Jun;46(8):1097-104.

质量控制

化学结构

Topiramate