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Statements

Subject Item
n2:DB00909
rdf:type
n3:Drug
n3:description
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.
n3:dosage
n13:271B5E14-363D-11E5-9242-09173F13E4C5 n13:271B5E12-363D-11E5-9242-09173F13E4C5 n13:271B5E13-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Murata M, Horiuchi E, Kanazawa I: Zonisamide has beneficial effects on Parkinson's disease patients. Neurosci Res. 2001 Dec;41(4):397-9. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11755227 # 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":http://www.ncbi.nlm.nih.gov/pubmed/12684361 # 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":http://www.ncbi.nlm.nih.gov/pubmed/15140322 # Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/15511691 # 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":http://www.ncbi.nlm.nih.gov/pubmed/12941455 # 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":http://www.ncbi.nlm.nih.gov/pubmed/18782051 # Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/20001433 # 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":http://www.ncbi.nlm.nih.gov/pubmed/18433351 # 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":http://www.ncbi.nlm.nih.gov/pubmed/7686468 # 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":http://www.ncbi.nlm.nih.gov/pubmed/14704463
n3:group
approved investigational
n3:halfLife
63 hours
n3:indication
For use as adjunctive treatment of partial seizures in adults with epilepsy.
n3:manufacturer
n8:271B5DFC-363D-11E5-9242-09173F13E4C5 n8:271B5DFD-363D-11E5-9242-09173F13E4C5 n8:271B5DFA-363D-11E5-9242-09173F13E4C5 n8:271B5DFB-363D-11E5-9242-09173F13E4C5 n8:271B5E00-363D-11E5-9242-09173F13E4C5 n8:271B5E01-363D-11E5-9242-09173F13E4C5 n8:271B5DFE-363D-11E5-9242-09173F13E4C5 n8:271B5DFF-363D-11E5-9242-09173F13E4C5 n8:271B5E04-363D-11E5-9242-09173F13E4C5 n8:271B5E05-363D-11E5-9242-09173F13E4C5 n8:271B5E02-363D-11E5-9242-09173F13E4C5 n8:271B5E03-363D-11E5-9242-09173F13E4C5 n8:271B5E08-363D-11E5-9242-09173F13E4C5 n8:271B5E09-363D-11E5-9242-09173F13E4C5 n8:271B5E06-363D-11E5-9242-09173F13E4C5 n8:271B5E07-363D-11E5-9242-09173F13E4C5 n8:271B5E0A-363D-11E5-9242-09173F13E4C5 n8:271B5E0B-363D-11E5-9242-09173F13E4C5
owl:sameAs
n17:DB00909 n30:DB00909
dcterms:title
Zonisamide
adms:identifier
n10:Zonisamide n20:10127 n21:5532 n22:10888 n23:D00538 n24:0378-6725-01 n25:DB00909 n26:C07504 n27:46505278 n28:PA451978 n29:5734
n3:mechanismOfAction
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.
n3:packager
n8:271B5DF8-363D-11E5-9242-09173F13E4C5 n8:271B5DF9-363D-11E5-9242-09173F13E4C5 n8:271B5DF6-363D-11E5-9242-09173F13E4C5 n8:271B5DF7-363D-11E5-9242-09173F13E4C5 n8:271B5DF4-363D-11E5-9242-09173F13E4C5 n8:271B5DF5-363D-11E5-9242-09173F13E4C5 n8:271B5DEF-363D-11E5-9242-09173F13E4C5 n8:271B5DF0-363D-11E5-9242-09173F13E4C5 n8:271B5DED-363D-11E5-9242-09173F13E4C5 n8:271B5DEE-363D-11E5-9242-09173F13E4C5 n8:271B5DEB-363D-11E5-9242-09173F13E4C5 n8:271B5DEC-363D-11E5-9242-09173F13E4C5 n8:271B5DE9-363D-11E5-9242-09173F13E4C5 n8:271B5DEA-363D-11E5-9242-09173F13E4C5 n8:271B5DE7-363D-11E5-9242-09173F13E4C5 n8:271B5DE8-363D-11E5-9242-09173F13E4C5 n8:271B5DE5-363D-11E5-9242-09173F13E4C5 n8:271B5DE6-363D-11E5-9242-09173F13E4C5 n8:271B5DE3-363D-11E5-9242-09173F13E4C5 n8:271B5DE4-363D-11E5-9242-09173F13E4C5 n8:271B5DE1-363D-11E5-9242-09173F13E4C5 n8:271B5DE2-363D-11E5-9242-09173F13E4C5 n8:271B5DDF-363D-11E5-9242-09173F13E4C5 n8:271B5DE0-363D-11E5-9242-09173F13E4C5 n8:271B5DDD-363D-11E5-9242-09173F13E4C5 n8:271B5DDE-363D-11E5-9242-09173F13E4C5 n8:271B5DDB-363D-11E5-9242-09173F13E4C5 n8:271B5DDC-363D-11E5-9242-09173F13E4C5 n8:271B5DF3-363D-11E5-9242-09173F13E4C5 n8:271B5DF1-363D-11E5-9242-09173F13E4C5 n8:271B5DF2-363D-11E5-9242-09173F13E4C5
n3:routeOfElimination
Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.
n3:synonym
Zonisamidum Zonisamida 1,2-Benzisoxazole-3-methanesulfonamide 3-(Sulfamoylmethyl)-1,2-benzisoxazole Benzo[D]isoxazol-3-yl-methanesulfonamide
n3:toxicity
Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.
n3:volumeOfDistribution
* 1.45 L/kg
n3:proteinBinding
40% (at concentrations of 1.0-7.0 µg/mL)
n3:synthesisReference
Tamar Nidam, "Novel sulfonation method for zonisamide intermediate in zonisamide synthesis and their novel crystal forms." U.S. Patent US20030114682, issued June 19, 2003.
n14:hasConcept
n15:M0077929
foaf:page
n6:zon1564.shtml n11:zonisamide.htm n31:zonisamide.html
n3:IUPAC-Name
n7:271B5E19-363D-11E5-9242-09173F13E4C5
n3:InChI
n7:271B5E1F-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n7:271B5E1E-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n7:271B5E1B-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n7:271B5E1C-363D-11E5-9242-09173F13E4C5
n3:SMILES
n7:271B5E1D-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n7:271B5E2F-363D-11E5-9242-09173F13E4C5 n7:271B5E17-363D-11E5-9242-09173F13E4C5
n3:logP
n7:271B5E31-363D-11E5-9242-09173F13E4C5 n7:271B5E18-363D-11E5-9242-09173F13E4C5 n7:271B5E15-363D-11E5-9242-09173F13E4C5
n3:logS
n7:271B5E16-363D-11E5-9242-09173F13E4C5
n3:pKa
n7:271B5E32-363D-11E5-9242-09173F13E4C5
n18:hasATCCode
n19:N03AX15
n3:H-Bond-Acceptor-Count
n7:271B5E25-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n7:271B5E26-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n7:271B5E20-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n7:271B5E21-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n7:271B5E23-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n7:271B5E22-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n7:271B5E24-363D-11E5-9242-09173F13E4C5
n3: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.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
68291-97-4
n3:category
n3: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]
n3:containedIn
n4:271B5E11-363D-11E5-9242-09173F13E4C5 n4:271B5E0F-363D-11E5-9242-09173F13E4C5 n4:271B5E10-363D-11E5-9242-09173F13E4C5 n4:271B5E0E-363D-11E5-9242-09173F13E4C5 n4:271B5E0D-363D-11E5-9242-09173F13E4C5 n4:271B5E0C-363D-11E5-9242-09173F13E4C5
n3:Bioavailability
n7:271B5E2B-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n7:271B5E2D-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n7:271B5E2E-363D-11E5-9242-09173F13E4C5
n3:Melting-Point
n7:271B5E30-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n7:271B5E2A-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n7:271B5E29-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n7:271B5E2C-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n7:271B5E1A-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-acidic-
n7:271B5E27-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n7:271B5E28-363D-11E5-9242-09173F13E4C5