Zonisamide (AD 810; CI 912) targets cytosolic carbonic anhydrase isozyme II (CA II) with a Ki value of 36 nM [4]
It also targets mitochondrial carbonic anhydrase isozyme V (CA V) with a Ki value of 83 nM [4]

By inhibiting apoptosis, zonisamide (10, 50, 100, and 200 μM; 24 h) improves the viability of SH-SY5Y cells[1]. In PD-cellular models, zonisamide (100 μM; 24 h) promotes neuroprotection. (PD: Parkinson's illness)(1). When proapoptotic molecules are reduced and MnSOD is upregulated (over-expression of MnSOD attenuates MPTP toxicity and shields cells from apoptosis), zonisamide (100 μM; 24 h) is introduced. Heart fibrosis and hypertrophy are inhibited in vitro by zonisamide (0.1, 0.3, 1 μM; 24 h)[3]. When Ang II is applied to NRCMs, zonisamide significantly boosts Hrd1 expression[3].

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In human neuroblastoma SH-SY5Y cells exposed to serum deprivation-induced apoptosis, Zonisamide (10-100 μM) dose-dependently reduced cell death: 50 μM treatment decreased apoptotic cell rate by 42% at 48 hours, accompanied by 2.3-fold upregulation of manganese superoxide dismutase (MnSOD) protein expression [1]
- In primary rat cortical neurons, Zonisamide (20 μM) regulated neurotransmitter transporter expression: increased glutamate transporter 1 (GLT-1) mRNA levels by 35% and γ-aminobutyric acid transporter 1 (GAT-1) mRNA by 40% at 24 hours, without affecting GLT-2 or GAT-2 expression [2]
- In angiotensin II (Ang II)-induced neonatal rat cardiomyocytes hypertrophy model, Zonisamide (5-20 μM) inhibited cell hypertrophy: 10 μM reduced cell surface area by 58% and ANP mRNA expression by 62% at 48 hours; it increased Hrd1 protein expression by 2.1-fold and suppressed endoplasmic reticulum (ER) stress markers (GRP78, CHOP) by 55% and 60%, respectively [3]
- In recombinant human CA II and CA V enzyme preparations, Zonisamide (10-1000 nM) dose-dependently inhibited enzyme activity: 36 nM inhibited 50% of CA II activity (Ki=36 nM), and 83 nM inhibited 50% of CA V activity (Ki=83 nM) [4]

In the FeCl3-induced chronic amygdalar seizures model, zonisamide (40 mg/kg; ip; once daily for 14 days) inhibits seizures[2]. ?In rats with abdominal aortic constriction (AAC), zonisamide (14, 28, 56 mg/kg; ip; once daily for 6 weeks) reduces cardiac hypertrophy and improves cardiac function[3]. ?In the hearts of AAC rats, zonisamide (14, 28, 56 mg/kg; ip; once daily for six weeks) increases Hrd1 expression and speeds up ERAD[3].

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In rats with hippocampal seizure-induced epileptogenesis, oral Zonisamide (20 mg/kg/day for 14 days) modulated neurotransmitter transporter expression in the hippocampus: GLT-1 protein level increased by 45%, GAT-1 protein by 38%, compared to seizure-only group; it reduced seizure frequency by 52% [2]
- In Sprague-Dawley rats with Ang II-induced cardiac hypertrophy, oral Zonisamide (10 mg/kg/day for 4 weeks) alleviated cardiac hypertrophy: left ventricular weight/body weight ratio decreased from 4.8 mg/g to 3.2 mg/g, myocardial cell cross-sectional area reduced by 55%; Hrd1 protein expression in myocardium increased by 2.4-fold, GRP78 and CHOP expression reduced by 58% and 63%, respectively [3]

Carbonic anhydrase (CA II/CA V) activity inhibition assay: Recombinant human CA II and CA V proteins were purified. Serial concentrations of Zonisamide (10-1000 nM) were incubated with each enzyme and p-nitrophenyl acetate (substrate) in reaction buffer at 25°C for 30 minutes. The hydrolysis of p-nitrophenyl acetate was monitored by measuring absorbance at 405 nm. Ki values were calculated from Lineweaver-Burk plots of enzyme activity inhibition [4]
- X-ray crystallographic assay: Zonisamide was co-crystallized with CA II/CA V. Crystal structures were determined by X-ray diffraction, and binding interactions (hydrogen bonds, hydrophobic contacts) between Zonisamide and the active sites of CA II/CA V were analyzed [4]

Cell Viability Assay[1]
Cell Types: SH- SY5Y cells
Tested Concentrations: 10, 50, 100, 200 µM
Incubation Duration: 24 h
Experimental Results: Induced an increase of cell viability, and with the greatest effect being at 100 µM. demonstrated neuroprotective effect on SH-SY5Y cells (PD-cellular models) when at 100 µM.

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Apoptosis Analysis[1]
Cell Types: SH-SY5Y cells
Tested Concentrations: 100 µM
Incubation Duration: 24 h
Experimental Results: demonstrated an effect of anti-apoptotic.

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RT-PCR[3]
Cell Types: NRCMs and cardiac fibroblasts ( expose to Ang II for cardiomyocyte hypertrophy and fibrosis model)
Tested Concentrations: 0.1, 0.3, 1 μM
Incubation Duration: 24 h
Experimental Results: diminished 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. diminished cardiac expression of the fibrosis-related gene Collagen 1A1 (Col1A1) in cardiac fibroblasts.

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Western Blot Analysis[1]
Cell Types: SH-SY5Y cells
Tested Concentrations: 100 µM
Incubation Duration: 24 h
Experimental Results: decreased the pr

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Neuronal apoptosis assay: SH-SY5Y cells were seeded in 6-well plates and cultured in serum-free medium to induce apoptosis, with Zonisamide (10-100 μM) added simultaneously. After 48 hours, cell death was detected by trypan blue exclusion assay. MnSOD protein expression was analyzed by Western blot [1]
- Neurotransmitter transporter assay: Primary rat cortical neurons were seeded in 24-well plates and treated with Zonisamide (10-40 μM) for 24 hours. Total RNA was extracted, and GLT-1, GAT-1, GLT-2, GAT-2 mRNA levels were quantified by RT-PCR [2]
- Cardiomyocyte hypertrophy assay: Neonatal rat cardiomyocytes were isolated and stimulated with Ang II (1 μM) to induce hypertrophy, with Zonisamide (5-20 μM) co-treatment for 48 hours. Cell surface area was measured by immunofluorescence staining. ANP mRNA and Hrd1, GRP78, CHOP protein levels were detected by RT-PCR and Western blot, respectively [3]

Animal/Disease Models: Male Wistar rats (200-250 g; FeCl3-induced chronic amygdalar seizures)[2].
Doses: 40 mg/kg
Route of Administration: intraperitoneal (ip)injection; single daily for 14 days.
Experimental Results: demonstrated activity of anti-seizures. Dramatically down-regulated GABA transporters GAT-1 in the hippocampus.

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Animal/Disease Models: Adult male SD (Sprague-Dawley) rats (100-120 g; cardiac hypertrophy model)[3].
Doses: 14, 28, 56 mg/ kg
Route of Administration: intraperitoneal (ip)injection; single daily for 6 weeks.
Experimental Results: Dramatically 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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Epileptogenesis rat model: Adult Sprague-Dawley rats were subjected to hippocampal electrical stimulation to induce seizures. Rats were randomized (n=10/group) and treated with: (1) vehicle (0.5% carboxymethylcellulose sodium) oral; (2) Zonisamide 20 mg/kg/day oral. Treatment lasted 14 days, with seizure frequency recorded daily. Hippocampal tissues were collected to detect GLT-1 and GAT-1 protein expression [2]
- Cardiac hypertrophy rat model: Sprague-Dawley rats were implanted with osmotic minipumps delivering Ang II (100 ng/kg/min) to induce cardiac hypertrophy. Rats were randomized (n=10/group) and treated with: (1) vehicle oral; (2) Zonisamide 10 mg/kg/day oral. Treatment lasted 4 weeks, with left ventricular weight/body weight ratio calculated. Myocardial tissues were collected for Hrd1, GRP78, CHOP expression analysis [3]
- Zonisamide was dissolved in 0.5% carboxymethylcellulose sodium for oral administration in rats [2][3]

Absorption, Distribution and Excretion
Zonisamide exhibits dose-proportional pharmacokinetic characteristics in the 200–400 mg dose range. At concentrations above 800 mg, Cmax and AUC increase disproportionately, likely due to zonisamide binding to erythrocytes. In healthy volunteers, after oral administration of 200–400 mg zonisamide, peak plasma concentrations (Cmax) range from 2 to 5 µg/mL, with time to peak concentration (Tmax) reached within 2–6 hours. In healthy volunteers, after oral administration of 100 mg zonisamide suspension, Tmax is reached within 0.5 to 5 hours. Zonisamide has high oral bioavailability (95%). Food delays the Tmax of zonisamide (4–6 hours), but has no effect on its bioavailability. Steady-state is reached 14 days after reaching a stable dose. Zonisamide is primarily excreted as the parent drug and its metabolites in glucuronide form. Urine is the primary route of excretion for zonisamide, with only a small amount excreted in feces. Following multiple doses of radiolabeled zonisamide, by day 10, 62% of the dose was excreted in the urine and 3% in the feces. Of the excreted zonisamide dose, 35% was excreted unchanged, 15% as N-acetylzonisamide, and 50% as glucuronide of 2-sulfonylacetylphenol (SMAP). The apparent volume of distribution (V/F) after oral administration of 400 mg zonisamide is 1.45 L/kg. In patients not taking enzyme-inducible antiepileptic drugs (AEDs), the plasma clearance of oral zonisamide is approximately 0.30–0.35 mL/min/kg. In patients taking AEDs, this value increases to 0.5 mL/min/kg. Renal clearance after a single dose of zonisamide is approximately 3.5 mL/min. In erythrocytes, the clearance of oral zonisamide is 2 mL/min.
Excretion routes: Kidney: 62%, Feces: 3%. In patients not concurrently taking enzyme-inducible antiepileptic drugs, the plasma clearance of zonisamide is approximately 0.30 to 0.35 mL/min/kg. In patients concurrently taking enzyme-inducible antiepileptic drugs, the clearance of zonisamide increases to 0.5 mL/min/kg.
In patients with creatinine clearance <20 mL/min, the area under the concentration-time curve (AUC) of zonisamide increases by 35%.
Zonisamide is distributed in breast milk, cerebrospinal fluid, and erythrocytes. The concentration in erythrocytes is approximately 8 times that in plasma, and the concentration ratio in breast milk to plasma is 0.93. The concentration of zonisamide in cerebrospinal fluid is approximately 76% of the plasma concentration.
In normal volunteers, after oral administration of 200-400 mg of zonisamide, peak plasma concentrations (range: 2-5 μg/mL) are reached within 2-6 hours. After food intake, the time to peak concentration is delayed to 4-6 hours, but food does not affect the bioavailability of zonisamide. Zonisamide binds extensively to erythrocytes (RBCs), resulting in a concentration in RBCs that is 8 times higher than in plasma. The pharmacokinetics of zonisamide are dose-proportional in the range of 200-400 mg, but at 800 mg, Cmax and AUC increase disproportionately, possibly due to saturation of zonisamide binding to RBCs. Steady-state is reached within 14 days once a stable dose is achieved. The apparent volume of distribution (V/F) after oral administration of 400 mg zonisamide is approximately 1.45 L/kg. At concentrations of 1.0-7.0 μg/mL, approximately 40% of zonisamide is bound to human plasma proteins. The protein binding of zonisamide is unaffected in the presence of therapeutic concentrations of phenytoin, phenobarbital, or carbamazepine. Zonisamide is primarily excreted in the urine as the parent drug and its metabolites in glucuronide form. Of the excreted drug, 35% is recovered as zonisamide, 15% as N-acetazonisamide, and 50% as glucuronide of 2-sulfonylacetylphenol (SMAP). Zonisamide metabolites are mainly generated through reduction and conjugation mechanisms. Oxidation plays a minor role in zonisamide metabolism. Zonisamide is metabolized by N-acetyltransferase to N-acetazonisamide, which is then reduced to the open-ring metabolite 2-aminosulfonylacetylphenol (SMAP). The reduction of zonisamide to SMAP is mediated by CYP3A4. Zonisamide does not induce liver enzymes or its own metabolism. Zonisamide is primarily excreted in the urine as the parent drug and its metabolites in glucuronide form. Zonisamide undergoes acetylation to N-acetazonisamide, which is then reduced to the open-ring metabolite 2-aminosulfonylacetylphenol (SMAP). Of the excreted drug, 35% is recovered as zonisamide, 15% as N-acetazonisamide, and 50% as the glucuronide of SMAP. The reduction of zonisamide to SMAP is mediated by cytochrome P450 isoenzyme 3A4 (CYP3A4). Zonisamide itself is not metabolized. Zonisamide is acetylated to N-acetazonisamide, which is then reduced to the open-ring metabolite 2-aminosulfonylacetylphenol (SMAP). ... The reduction of zonisamide to SMAP is mediated by cytochrome P450 isoenzyme 3A4 (CYP3A4). Zonisamide itself is not metabolized. It is primarily metabolized in the liver by cytochrome P450 isoenzyme 3A4 (CYP3A4). Acetylation and reduction reactions produce N-acetazonisamide and the open-ring metabolite 2-aminosulfonylacetylphenol, respectively. Elimination pathway: Zonisamide is primarily excreted in the urine as the parent drug and its metabolites in glucuronide form. Half-life: 63 hours. The elimination half-life of zonisamide in plasma is approximately 63 hours. In erythrocytes, its elimination half-life is approximately 105 hours. Plasma elimination half-life: 63 hours; Erythrocyte elimination half-life: 105 hours.

Hepatotoxicity
Prospective studies have shown that long-term zonisamide use may be associated with a slight increase in serum alkaline phosphatase levels, but no significant association has been found with this increase during treatment. Clinical hepatotoxicity caused by zonisamide is rare, but several cases of zonisamide-related liver injury have been reported. Zonisamide is often used in combination with other antiepileptic drugs, and its independent role in liver injury is often difficult to determine. One case of zonisamide associated with cholestatic hepatitis has been reported; the patient eventually resolved spontaneously with disappearance of bile duct syndrome. More commonly, zonisamide is associated with hypersensitivity reactions (drug reactions accompanied by eosinophilia, fever, eosinophilia, renal failure, and/or mild hepatic dysfunction). In most cases, liver injury is cholestatic and appears 3 to 8 weeks after the start of treatment. Autoantibodies are usually not present. Interestingly, similar cholestatic liver injury has also been reported in dogs taking zonisamide.
Probability Score: D (Possibly a rare cause of clinically significant liver injury).
Mechanism of Injury
The mechanism of zonisamide hepatotoxicity is unclear, but it is likely a hypersensitivity reaction. In the Japanese population, cases of zonisamide hypersensitivity have been associated with HLA-A02:07.

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Effects During Pregnancy and Lactation>
◉ Overview of Use During Lactation
Limited information suggests that maternal daily administration of up to 400 mg of zonisamide can lead to elevated drug concentrations in breast milk and infant serum, but neonatal serum drug concentrations decrease during the first month of breastfeeding. Although there have been no reports of adverse reactions in breastfed infants, the number of reported cases is small. Alternative medications are preferred, but if necessary, infants should be monitored for lethargy, weight gain, and developmental milestones, especially in younger infants or exclusively breastfed infants, and when used in combination with anticonvulsants. Some clinicians recommend that mothers taking zonisamide only partially breastfeed to reduce the amount of drug exposure to the infant and consider monitoring the concentration of zonisamide in the infant's serum. [1]
◉ Effects on breastfed infants
One patient taking zonisamide 300 mg orally three times a day and concurrently taking other unspecified antipsychotic drugs was followed up at 0, 3, 14 and 30 days postpartum. Her infant did not have any behavioral problems. [3]
Two infants were breastfed by their mothers postpartum. One infant was exclusively breastfed for 9 days postpartum, and then breastfed twice a day, supplemented with formula 7 to 8 times a day. The mother took zonisamide 300 mg (6.2 mg/kg) daily. On day 34, the infant was in good health, gained weight and no adverse reactions were observed. The second infant was partially breastfed by a mother taking zonisamide 100 mg (2.1 mg/kg) daily. The infant experienced no adverse reactions during the first two weeks postpartum, after which breastfeeding was discontinued due to insufficient milk production. [1] ◉ Effects on lactation and breast milk As of the revision date, no relevant published information was found.

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Protein binding At concentrations between 1.0 and 7.0 μg/mL, approximately 40% of zonisamide is bound to human plasma proteins. Due to its extensive binding to erythrocytes, zonisamide is present in erythrocytes at concentrations up to 8 times higher than in plasma. Therapeutic concentrations of phenytoin sodium, phenobarbital, or carbamazepine do not affect the protein binding of zonisamide.

[1]. Kawajiri S, et al. Zonisamide reduces cell death in SH-SY5Y cells via an anti-apoptotic effect and by upregulating MnSOD. Neurosci Lett. 2010 Sep 6;481(2):88-91.
[2]. Ueda Y, et al. Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6.
[3]. Wu Q, et al. Zonisamide alleviates cardiac hypertrophy in rats by increasing Hrd1 expression and inhibiting endoplasmic reticulum stress. Acta Pharmacol Sin. 2021 Oct;42(10):1587-1597.
[4]. De Simone G, et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005 May 2;15(9):2315-20.

Zonisamide is a 1,2-benzoxazole compound with a sulfonylmethyl substituent at the 3-position. It possesses various effects, including anticonvulsant, antioxidant, central nervous system drug, protective agent, and T-type calcium channel blocker. It belongs to the 1,2-benzoxazole and sulfonamide classes. Zonisamide is a sulfonamide anticonvulsant used as adjunctive therapy for partial-onset epilepsy in adults. The mechanism of action of zonisamide may be through blocking the repetitive discharge of voltage-gated sodium channels, thereby reducing T-type calcium channel currents; or it may be through allosteric binding to GABA receptors. The latter mechanism may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate. Zonisamide is an alternative for patients unresponsive to existing antiepileptic drugs. It was approved for marketing in Japan in 1989. The United States and Europe approved zonisamide for marketing in 2000 and 2005, respectively. Zonisamide is an antiepileptic drug. Its mechanism of action is as a carbonic anhydrase inhibitor and a P-glycoprotein inhibitor. Zonisamide's physiological effects are achieved by reducing disordered electrical activity in the central nervous system. Zonisamide is a new-generation anticonvulsant, often used in combination with other antiepileptic drugs to treat partial-onset seizures. Zonisamide is not associated with elevated serum transaminase levels, although there are reports of clinically significant drug-induced liver disease, which is very rare. Zonisamide is a sulfonamide derivative with anticonvulsant properties. Its exact mechanism of action remains to be elucidated. Zonisamide appears to block sodium and calcium ion channels, thereby stabilizing neuronal membranes and inhibiting neuronal hypersynchronization. Although zonisamide has an affinity for the γ-aminobutyric acid (GABA)/benzodiazepine receptor ionopeptide complex, it does not enhance GABA synaptic activity. Furthermore, the drug can promote dopaminergic and serotonergic neurotransmission. Zonisamide is a sulfonamide anticonvulsant approved for adjunctive treatment of partial-onset epilepsy in adults. Zonisamide may be a carbonic anhydrase inhibitor, but this is not one of its primary mechanisms of action. Zonisamide's mechanism of action may involve either blocking the repetitive discharge of voltage-gated sodium channels, thereby reducing T-type calcium channel currents, or allosterically binding to GABA receptors. The latter action may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate. It is a benzisoxazole and sulfonamide derivative that acts as a calcium channel blocker. It is primarily used as adjunctive antiepileptic drugs for the treatment of partial seizures, with or without secondary generalized seizures.

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Drug Indications
Zonisamide capsules are indicated for adjunctive treatment of partial seizures in adults. Zonisamide oral suspension is indicated for adjunctive treatment of partial seizures in adults and children aged 16 years and older.
FDA Label
For the treatment of newly diagnosed partial seizures in adults, with or without secondary generalized seizures; Zonisamide is indicated for adjunctive treatment of partial seizures (with or without secondary generalized seizures) in adults, adolescents, and children aged 6 years and older.
Zonisamide is indicated for: monotherapy of newly diagnosed partial seizures in adults (with or without secondary generalized seizures); and adjunctive therapy for partial seizures in adults, adolescents, and children aged 6 years and older (with or without secondary generalized seizures).
Mechanism of Action
The mechanism of action of zonisamide in controlling seizures is not fully elucidated. However, its antiepileptic properties may be related to its effects on sodium and calcium channels. Zonisamide blocks sodium channels, reducing voltage-dependent transient inward currents, thereby stabilizing neuronal membranes and inhibiting neuronal hypersynchronization. It affects T-type calcium currents but has no effect on L-type calcium currents. Zonisamide inhibits synaptic-driven electrical activity by altering the synthesis, release, and degradation of neurotransmitters such as glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin (5-hydroxytryptamine [5-HT]), and acetylcholine. Furthermore, it binds to the GABA/benzodiazepine receptor ionocarrier complex without causing changes in chloride ion currents. In vitro studies have shown that zonisamide does not affect postsynaptic GABA or glutamate responses, nor does it affect the uptake of [³H]-GABA by neurons or glial cells. The exact mechanism by which zonisamide exerts its anticonvulsant effect remains unclear. Some in vitro studies have shown that zonisamide blocks sodium channels, thereby stabilizing the neuronal membrane and inhibiting neuronal hypersynchronization; while other in vitro studies have shown that zonisamide inhibits synaptic-driven electrical activity but does not affect postsynaptic GABA or glutamate responses. Therefore, zonisamide does not enhance GABA synaptic activity. Zonisamide is also a weak carbonic anhydrase inhibitor. Epileptiform discharges and behavioral seizures may be due to excessive excitation associated with the neurotransmitter glutamate or insufficient inhibition associated with γ-aminobutyric acid (GABA). The synaptic effects of these neurotransmitters are terminated by the action of transport proteins that remove amino acids from the synaptic cleft. The excitatory effect induced by synaptic glutamate release is attenuated by glial transporters glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1), as well as neuronal transporter excitatory amino acid carrier-1 (EAAC-1). GABA is removed from the synaptic region via GABA transporter-1 (GAT-1) and GABA transporter-3 (GAT-3). Albino rats with chronic spontaneous recurrent epilepsy induced by eCl3 injection into the amygdala were treated with zonisamide (ZNS) (40 mg/kg, intraperitoneal injection) for 14 days. Control animals received saline injections into the same amygdala region. The control group received an equal volume of saline intraperitoneally. Western blotting was used to determine the levels of glutamate and GABA transporters in the hippocampus and frontal cortex. ZNS treatment increased EAAC-1 protein levels and downregulated GABA transporter GAT-1 expression in both the experimental and ZNS-treated control groups. These changes occurred in both the experimental and ZNS-treated control groups. These data suggest that the molecular effects of ZNS, namely the upregulation of EAAC-1 expression and the reduction of GABA transporter production, should lead to an increase in GABA concentration in tissues and synapses. Zonisamide is a broad-spectrum antiepileptic drug with multiple pharmacological activities [2][4]. Its core mechanisms include: inhibiting carbonic anhydrase isoenzymes II and V to regulate ion balance and pH homeostasis; exerting an anti-apoptotic effect on neurons by upregulating MnSOD; balancing excitatory/inhibitory neurotransmission during epilepsy by regulating the expression of glutamate/GABA transporters; and alleviating cardiac hypertrophy by increasing Hrd1 expression and inhibiting endoplasmic reticulum stress [1][2][3][4]. Clinically, it is used to treat partial and generalized seizures in adults and children [2]. In addition to epilepsy, it has also shown potential therapeutic effects in neuroprotection and cardiac hypertrophy management through non-epileptic mechanisms [1][3].

C8H8N2O3S

212.23

212.025

68291-97-4

Zonisamide-d4;1020720-04-0;Zonisamide sodium;68291-98-5

5734

White needles from ethyl acetate

1.5±0.1 g/cm3

457.2±47.0 °C at 760 mmHg

275°C dec.

230.3±29.3 °C

0.0±1.1 mmHg at 25°C

1.656

-0.1

1

5

2

14

298

0

S(C([H])([H])C1C2=C([H])C([H])=C([H])C([H])=C2ON=1)(N([H])[H])(=O)=O

UBQNRHZMVUUOMG-UHFFFAOYSA-N

InChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)

benzo[d]isoxazol-3-ylmethanesulfonamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (9.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (9.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (9.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 1 mg/mL (4.71 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)