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药品详细

Zonisamide(唑尼沙胺)

化学结构式图
中文名
唑尼沙胺
英文名
Zonisamide
分子式
C8H8N2O3S
化学名
1,2-benzoxazol-3-ylmethanesulfonamide
分子量
Average: 212.226
Monoisotopic: 212.025562822
CAS号
68291-97-4
ATC分类
N03A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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.

生产厂家
  • Alphapharm party ltd
  • Apotex inc etobicoke site
  • Banner pharmacaps inc
  • Barr laboratories inc
  • Corepharma llc
  • Dr reddys laboratories ltd
  • Eisai inc
  • Glenmark generics inc usa
  • Invagen pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Wockhardt ltd
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Murata M, Horiuchi E, Kanazawa I: Zonisamide has beneficial effects on Parkinson’s disease patients. Neurosci Res. 2001 Dec;41(4):397-9. Pubmed
  2. Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR: Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003 Apr 9;289(14):1820-5. Pubmed
  3. Hasegawa H: Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital. Curr Med Res Opin. 2004 May;20(5):577-80. Pubmed
  4. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. Pubmed
  5. Ueda Y, Doi T, Tokumaru J, Willmore LJ: 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. Pubmed
  6. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. Pubmed
  7. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. Pubmed
  8. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. Pubmed
  9. Peters DH, Sorkin EM: Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs. 1993 May;45(5):760-87. Pubmed
  10. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzoxazoles
Substructures
  • Sulfonyls
  • Benzene and Derivatives
  • Isoxazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Oxazoles
  • Sulfonamides
  • Imines
  • Benzoxazoles
适应症
药理
Indication For use as adjunctive treatment of partial seizures in adults with epilepsy.
Pharmacodynamics Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and calcium channels, which leads to the suppression of neuronal hypersynchronization (i.e. convulsions). Sonisamide has also been found to potentiate dopaminergic and serotonergic neurotransmission but does not appear to potentiate syanptic activity by GABA (gamma amino butyric acid).
Mechanism of action Zonisamide binds to sodium channels and voltage sensitive calcium channels, which suppresses neuronal depolarization and hypersynchronization. Zonisamide also inhibits carbonic anhydrase to a weaker extent, but such an effect is not thought to contribute substantially to the drug's anticonvulsant activity.
Absorption Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide.
Volume of distribution
  • 1.45 L/kg
Protein binding 40% (at concentrations of 1.0-7.0 µg/mL)
Metabolism
Primarily hepatic through cytochrome P450 isoenzyme 3A4 (CYP3A4). Undergoes acetylation and reduction, forming N-acetyl zonisamide, and the open-ring metabolite 2–sulfamoylacetyl phenol, respectively.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Zonisamide
2-sulfamoylacetylphenol Details
Zonisamide
    		N-acetyl zonisamide Details
    Route of elimination Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.
    Half life 63 hours
    Clearance
    • 0.30 – 0.35 mL/min/kg [patients not receiving enzyme-inducing antiepilepsy drugs (AEDs)]
    • 0.35 – 0.5 mL/min/kg [Concomitant administration of phenytoin and carbamazepine]
    Toxicity Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 161-163 °C Not Available
    water solubility 0.8 mg/mL Not Available
    logP 0.5 Not Available
    pKa 10.2 Not Available
    Predicted Properties
    Property Value Source
    water solubility 2.09e+00 g/l ALOGPS
    logP 0.67 ALOGPS
    logP 0.11 ChemAxon
    logS -2 ALOGPS
    pKa (strongest acidic) 9.84 ChemAxon
    pKa (strongest basic) -1.8 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 3 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 86.19 ChemAxon
    rotatable bond count 2 ChemAxon
    refractivity 50.3 ChemAxon
    polarizability 19.48 ChemAxon
    药物相互作用
    Drug Interaction
    Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if amprenavir is initiated, discontinued or dose changed.
    Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if atazanavir is initiated, discontinued or dose changed.
    Brinzolamide As both brinzolamide and zonisamide are carbonic anhydrase inhibitors, there is an increased risk of adverse effects.The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Avoid concurrent use of different carbonic anhydrase inhibitors when possible.
    Clarithromycin Clarithromcyin, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if clarithromycin is initiated, discontinued or dose changed.
    Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if conivaptan is initiated, discontinued or dose changed.
    Darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if darunavir is initiated, discontinued or dose changed.
    Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if delavirdine is initiated, discontinued or dose changed.
    Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if fosamprenavir is initiated, discontinued or dose changed.
    Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if imatinib is initiated, discontinued or dose changed.
    Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if indinavir is initiated, discontinued or dose changed.
    Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if isoniazid is initiated, discontinued or dose changed.
    Itraconazole Itraconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if itraconazole is initiated, discontinued or dose changed.
    Ketoconazole Ketonconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if ketoconazole is initiated, discontinued or dose changed.
    Lopinavir Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if lopinavir is initiated, discontinued or dose changed.
    Mefloquine Mefloquine may decrease the serum concentration and therapeutic effect of zonisamide. Concomitant therapy is contraindicated in patients with history of convulsions.
    Methotrimeprazine Additive CNS depressant effects. Reduce zonisamide dose by half upon initiation of methotrimeprazine. Zonisamide dose may be adjusted once methotrimeprazine dose has been established. Monitor for increased CNS depression.
    Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nefazodone is initiated, discontinued or dose changed.
    Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nelfinavir is initiated, discontinued or dose changed.
    Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if nicardipine is initiated, discontinued or dose changed.
    Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if posaconazole is initiated, discontinued or dose changed.
    Quinidine Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if quinidine is initiated, discontinued or dose changed.
    Ritonavir Ritonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if ritonavir is initiated, discontinued or dose changed.
    Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if saquinavir is initiated, discontinued or dose changed.
    Telithromycin Telithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if telithromycin is initiated, discontinued or dose changed.
    Triprolidine The CNS depressants, Triprolidine and Zonisamide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
    Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if voriconazole is initiated, discontinued or dose changed.
    食物相互作用
    Not Available

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