Topiramate is an orally active sulfa-derivative monosaccharide with a broad spectrum of antiepileptic activity [1]. Topiramate can increase cerebral GABA concentrations, enhancing the inhibitory GABAergic transmission by binding to allosteric GABA-A receptors, and can inhibit brain glutamate release by antagonizing AMPA kainate type of glutamate receptors [2]. Topiramate has been widely used to prevent epileptic seizures and to alleviate obesity and alcohol dependence[3].
In vitro, Topiramate (1500µM) treatment for 72 hours significantly inhibited the proliferation of SKOV3 cells and reduced the protein expressions of CDK4, CDK6, and cyclin D1[4]. Treatment with 100µg/ml Topiramate for 24 hours significantly reduced the release of IL-1β and IL-6 in primary rat microglial cells stimulated by lipopolysaccharide (LPS) [5].
In vivo, Topiramate treatment via daily subcutaneous injection at a dose of 90mg/kg/day for 8 days significantly reduced the ethanol intake of C57BL/6 mice[6]. A single intraperitoneal injection of a 100mg/kg dose of Topiramate for 2 hours significantly increased the survival rate of rats with status epilepticus and enhanced the survival rate of CA1 and CA3 pyramidal cells[7]. One hour before intracerebroventricular injection of kainic acid (KA) (0.1µg), a single intraperitoneal injection of a 100mg/kg dose of Topiramate could alleviate neuronal cell death caused by epileptic seizures in mice and reduce the p-Erk immunoreactivity in the CA3 region of the hippocampus induced by KA [8].
References:
[1] Abtahi M A, Abtahi S H, Fazel F, et al. Topiramate and the vision: a systematic review[J]. Clinical Ophthalmology, 2012: 117-131.
[2] Arnone D. Review of the use of topiramate for treatment of psychiatric disorders[J]. Annals of general psychiatry, 2005, 4(1): 5.
[3] Mirza N, Marson A G, Pirmohamed M. Effect of topiramate on acid–base balance: extent, mechanism and effects[J]. British journal of clinical pharmacology, 2009, 68(5): 655-661.
[4] Xu G, Fang Z, Clark L H, et al. Topiramate exhibits anti-tumorigenic and metastatic effects in ovarian cancer cells[J]. American journal of translational research, 2018, 10(6): 1663.
[5] Andrzejczak D, Woldan-Tambor A, Bednarska K, et al. The effects of topiramate on lipopolysaccharide (LPS)-induced proinflammatory cytokine release from primary rat microglial cell cultures[J]. Epilepsy Research, 2016, 127: 352-357.
[6] Nguyen S A, Malcolm R, Middaugh L D. Topiramate reduces ethanol consumption by C57BL/6 mice[J]. Synapse, 2007, 61(3): 150-156.
[7] Kudin A P, Debska‐Vielhaber G, Vielhaber S, et al. The mechanism of neuroprotection by topiramate in an animal model of epilepsy[J]. Epilepsia, 2004, 45(12): 1478-1487.
[8] Park H J, Kim H J, Park H J, et al. Protective effect of topiramate on kainic acid–induced cell death in mice hippocampus[J]. Epilepsia, 2008, 49(1): 163-167.
Topiramate是一种口服有效的磺胺衍生单糖，具有广谱抗癫痫活性[1]。Topiramate可增加脑内GABA浓度，通过变构结合GABA-A受体增强抑制性GABA能传递，并可拮抗AMPA红藻氨酸型谷氨酸受体，从而抑制脑内谷氨酸释放[2]。Topiramate已被广泛用于预防癫痫发作，以及减轻肥胖和酒精依赖[3]。
在体外，1500µM的Topiramate处理SKOV3细胞72小时，显著抑制了细胞增殖，并降低了CDK4、CDK6和细胞周期蛋白D1的蛋白表达[4]。100µg/ml的Topiramate处理原代大鼠小胶质细胞24小时，显著降低了脂多糖刺激的IL-1β和IL-6的释放[5]。
在体内，每日皮下注射90mg/kg/day剂量的Topiramate，连续8天，显著减少了C57BL/6小鼠的乙醇摄入量[6]。单次腹腔注射100mg/kg剂量的Topiramate，作用2小时，显著提高了癫痫持续状态大鼠的存活率，并增强了CA1和CA3锥体细胞的存活率[7]。在脑室内注射红藻氨酸前1小时，单次腹腔注射100mg/kg剂量的Topiramate，可减轻小鼠癫痫发作引起的神经元细胞死亡，并降低KA诱导的海马CA3区p-Erk免疫反应性[8]。