Zonisamide (AD 810) 是一种口服有效的碳酸酐酶 (carbonic anhydrase) 抑制剂，对人类线粒体同工酶hCA II和hCA V的Ki值分别为 35.2 nM 和 20.6 nM。Zonisamide 可通过抗细胞凋亡和上调MnSOD水平来发挥神经保护作用。Zonisamide 还能增加Hrd1的表达，从而改善 AAC 大鼠的心脏功能。Zonisamide 可用于癫痫、帕金森和心脏肥大的研究。
| 生物活性 | Zonisamide (AD 810) is an orally activecarbonic anhydraseinhibitor, withKis of 35.2 and 20.6 nM forhCA IIandhCA V, respectively. Zonisamide exerts neuroprotective effects through anti-apoptosisand upregulatingMnSODlevels. Zonisamide also increases the expression ofHrd1, thereby improving cardiac function in AAC rats. Zonisamide can be used in studies of seizure, parkinson’s disease and cardiac hypertrophy[1][2][3][4]. |
| IC50& Target | Ki: 35.2 nM (hCA II) , 20.6 nM (hCA V)[4]. |
体外研究
(In Vitro) | Zonisamide (10, 50, 100, 200 μM; 24 h) increases viability of SH-SY5Y cells via an anti-apoptotic effect[1].
Zonisamide (100 μM; 24 h) shows neuroprotective effects in PD-cellular models. (PD: parkinson’s disease)[1].
Zonisamide (100 μM; 24 h) reduces levels of proapoptotic molecules, and upregulates levels of MnSOD (MnSOD over-expression attenuates MPTP toxicity and protects cells from apoptosis)[1].
Zonisamide (0.1, 0.3, 1 μM; 24 h) inhibits cardiac hypertrophy and fibrosis in vitro[3].
Zonisamide markedly increases the expression of Hrd1 in Ang II-treated NRCMs[3].
Cell Viability Assay[1] | Cell Line: | SH-SY5Y cells | | Concentration: | 10, 50, 100, 200 μM | | Incubation Time: | 24 h | | Result: | Induced an increase of cell viability, and with the greatest effect being at 100 μM.
Exhibited neuroprotective effect on SH-SY5Y cells (PD-cellular models) when at 100 μM. |
Apoptosis Analysis[1] | Cell Line: | SH-SY5Y cells | | Concentration: | 100 μM | | Incubation Time: | 24 h | | Result: | Showed an effect of anti-apoptotic. |
RT-PCR[3] | Cell Line: | NRCMs and cardiac fibroblasts (expose to Ang II for cardiomyocyte hypertrophy and fibrosis model) | | Concentration: | 0.1, 0.3, 1 μM | | Incubation Time: | 24 h | | Result: | Decreased the expression of atrial natriuretic factor (ANF) and cardiomyosin heavy chain β (β-MHC) but increased the expression of cardiac myosin heavy chain α (α-MHC) in NRCMs.
Decreased cardiac expression of the fibrosis-related gene Collagen 1A1 (Col1A1) in cardiac fibroblasts. |
Western Blot Analysis[1] | Cell Line: | SH-SY5Y cells | | Concentration: | 100 μM | | Incubation Time: | 24 h | | Result: | Reduced the proapoptotic molecules levels of cleaved caspase-9, -3, and p-JNK, and blocked the activation of proapoptotic molecules in SH-SY5Y cells.
Induced an increase in MnSOD levels.(MnSOD over-expression attenuates MPTP toxicity and protects cells from apoptosis). |
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体内研究
(In Vivo) | Zonisamide (40 mg/kg; i.p.; single daily for 14 days) prevents seizures in FeCl3-induced chronic amygdalar seizures model[2].
Zonisamide (14, 28, 56 mg/kg; i.p.; single daily for 6 weeks) alleviates cardiac hypertrophy and improved cardiac function in rats subjected to AAC (abdominal aortic constriction)[3].
Zonisamide (14, 28, 56 mg/kg; i.p.; single daily for 6 weeks) upregulates Hrd1 expression and accelerates ERAD in the hearts of AAC rats[3].
| Animal Model: | Male Wistar rats (200-250 g; FeCl3-induced chronic amygdalar seizures)[2]. | | Dosage: | 40 mg/kg | | Administration: | Intraperitoneal injection; single daily for 14 days. | | Result: | Showed activity of anti-seizures.
Significantly down-regulated GABA transporters GAT-1 in the hippocampus. |
| Animal Model: | Adult male Sprague-Dawley rats (100-120 g; cardiac hypertrophy model)[3]. | | Dosage: | 14, 28, 56 mg/kg | | Administration: | Intraperitoneal injection; single daily for 6 weeks. | | Result: | Significantly attenuated cardiac hypertrophy and fibrosis.
Increased LV ejection fraction (EF), fractional shortening (FS) and E/A ratio.
Markedly increased the expression of Hrd1 in the hearts of AAC rats. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 250 mg/mL(1177.97 mM;Need ultrasonic) H2O : 0.67 mg/mL(3.16 mM;Need ultrasonic) 配制储备液 | 1 mM | 4.7119 mL | 23.5593 mL | 47.1187 mL | | 5 mM | 0.9424 mL | 4.7119 mL | 9.4237 mL | | 10 mM | 0.4712 mL | 2.3559 mL | 4.7119 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
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此方案可获得 ≥ 2.08 mg/mL (9.80 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (9.80 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (9.80 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (9.80 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (9.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 4. 请依序添加每种溶剂： PBS Solubility: 1 mg/mL (4.71 mM); Clear solution; Need ultrasonic and warming and heat to 60℃ *以上所有助溶剂都可在本网站选购。
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