Zonisamide

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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。

Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures. Zonisamide may be a carbonic anhydrase inhibitor although this is not one of the primary mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels leading to a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate. (In Vitro):Zonisamide (10, 50, 100, 200 μM; 24 h) increases viability of SH-SY5Y cells via an anti-apoptotic effect.Zonisamide (100 μM; 24 h) shows neuroprotective effects in PD-cellular models. (PD: parkinson’s disease).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).Zonisamide (0.1, 0.3, 1 μM; 24 h) inhibits cardiac hypertrophy and fibrosis in vitro.Zonisamide markedly increases the expression of Hrd1 in Ang II-treated NRCMs.(In Vivo):Zonisamide (40 mg/kg; i.p.; single daily for 14 days) prevents seizures in FeCl3-induced chronic amygdalar seizures model.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).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.

Zonisamide (10, 50, 100, 200 μM; 24 h) increases viability of SH-SY5Y cells via an anti-apoptotic effect.Zonisamide (100 μM; 24 h) shows neuroprotective effects in PD-cellular models. (PD: parkinson’s disease).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).Zonisamide (0.1, 0.3, 1 μM; 24 h) inhibits cardiac hypertrophy and fibrosis in vitro.Zonisamide markedly increases the expression of Hrd1 in Ang II-treated NRCMs.Cell Viability Assay 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 Cell Line:SH-SY5Y cells Concentration:100 μM Incubation Time:24 h Result:Showed an effect of anti-apoptotic.RT-PCR 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 Cell Line:SH-SY5Y cells Concentration:100 μM Incubation Time:24 hResult: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).

Zonisamide (40 mg/kg; i.p.; single daily for 14 days) prevents seizures in FeCl3-induced chronic amygdalar seizures model.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).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. Animal Model:Male Wistar rats (200-250 g; FeCl3-induced chronic amygdalar seizures).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).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.

CI-912 | PD 110843

GPCR/G Protein

Calcium Channel

Calcium Channel| Carbonic anhydrase| Sodium Channel

Neurological Disease

——

68291-97-4

212.23

C8H8N2O3S

>98% (HPLC)

Ethanol: 5 mg/mL (23.55 mM); DMSO: 42 mg/mL (197.89 mM)

O=S(CC1=NOC2=CC=CC=C12)(N)=O

benzo[d]isoxazol-3-ylmethanesulfonamide

(-20℃)

With Ice Pack

≥ 2 years