Topiramate (T3D2733)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2009-07-21 20:26:27 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2733
Identification
Common NameTopiramate
ClassSmall Molecule
DescriptionTopiramate is an anticonvulsant drug used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, although it is not FDA approved for this purpose and such use is somewhat controversial. This drug has been investigated for use in treatment of obesity, especially to aid in the reduction of binge eating, and also as a possible treatment for alcoholism. However, these uses are not actively promoted by the manufacturer, and like its use for bipolar disorder, are 'off-label' uses. The drug is also used in clinical trials to treat Post Traumatic Stress Disorder. A pilot study suggests that Topiramate is possibly effective against infantile spasm; Chemically, topiramate is a sulfamate-substituted monosaccharide, related to fructose, a rather unusual chemical structure for an anticonvulsant. Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine as unchanged drug. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particularly subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secondarily generalized tonic-clonic seizures in the kindling model, findings predictive of a broad spectrum of antiseizure activities clinically; Johnson. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, although it is not FDA approved for this purpose and such use is somewhat controversial. This drug has been investigated for use in treatment of obesity, especially to aid in the reduction of binge eating, and also as a possible treatment for alcoholism. However, these uses are not actively promoted by the manufacturer, and like its use for bipolar disorder, are 'off-label' uses. The drug is also used in clinical trials to treat Post Traumatic Stress Disorder. A pilot study suggests that Topiramate is possibly effective against infantile spasm. In May 2006 the U.S. National Institutes of Health web site clinicaltrials.gov listed several studies sponsored by Ortho-McNeil which propose to examine the use of topiramate on migraine, cluster, and severe headaches within various demographics; Topiramate (brand name: Topamax) is an anticonvulsant drug produced by Ortho-McNeil, a division of Johnson & Topiramate (brand name: Topamax) is an anticonvulsant drug produced by Ortho-McNeil, a division of Johnson & Johnson. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, although it is not FDA approved for this purpose and such use is somewhat controversial. This drug has been investigated for use in treatment of obesity, especially to aid in the reduction of binge eating, and also as a possible treatment for alcoholism. However, these uses are not actively promoted by the manufacturer, and like its use for bipolar disorder, are 'off-label' uses. The drug is also used in clinical trials to treat Post Traumatic Stress Disorder. A pilot study suggests that Topiramate is possibly effective against infantile spasm. In May 2006 the U.S. National Institutes of Health web site clinicaltrials.gov listed several studies sponsored by Ortho-McNeil which propose to examine the use of topiramate on migraine, cluster, and severe headaches within various demographics.
Compound Type
  • Anti-Obesity Agent
  • Anticonvulsant
  • Drug
  • Food Toxin
  • Metabolite
  • Neuroprotective Agent
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
2,3:4,5-Di-O-isopropylidene-beta-D-fructopyranose sulfamate
Epitomax
McN-4853
QUDEXY
RWJ-17021
Tipiramate
Tipiramato
Topamax
Topamax Sprinkle
Topiramato
Topiramatum
Topiramic acid
Topomax
TPM
Trokendi XR
Chemical FormulaC12H21NO8S
Average Molecular Mass339.362 g/mol
Monoisotopic Mass339.099 g/mol
CAS Registry Number97240-79-4
IUPAC Name[(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0²,⁶]dodecan-6-yl]methyl sulfamate
Traditional Nametopiramate
SMILES[H][C@@]12CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@]3([H])[C@]1([H])OC(C)(C)O2
InChI IdentifierInChI=1S/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1
InChI KeyInChIKey=KJADKKWYZYXHBB-XBWDGYHZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dioxolopyrans. Dioxolopyrans are compounds containing a dioxolopyran moiety, which consists of a dioxole ring fused to a pyran ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDioxolopyrans
Sub ClassNot Available
Direct ParentDioxolopyrans
Alternative Parents
Substituents
  • Dioxolopyran
  • Ketal
  • Oxane
  • Monosaccharide
  • Organic sulfuric acid or derivatives
  • Meta-dioxolane
  • Oxacycle
  • Acetal
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Prostate
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point125 - 126°C
Boiling PointNot Available
Solubility9.8 mg/mL
LogP-0.7
Predicted Properties
PropertyValueSource
Water Solubility6.8 g/LALOGPS
logP1.29ALOGPS
logP0.13ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)11.09ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area115.54 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.3 m³·mol⁻¹ChemAxon
Polarizability32.42 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-003r-5893000000-57939ef42b569234ad292017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03di-0239000000-994a7b97e101c455a7922017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-01x0-1970000000-f0e80f5cc5d6fc2b6d382017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-01q9-2960000000-a11a150bcada5055d2e92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-014i-0090000000-c1fa3d6ff15890fc14182017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-00di-0059000000-a6337903cab01edce60e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0239000000-994a7b97e101c455a7922017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-01x0-1970000000-f0e80f5cc5d6fc2b6d382017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-004i-9000000000-a8df5a6ea132d69b94892021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-004i-9000000000-f76d8f2283f18dfa20be2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-004i-9000000000-316320612e65b9d317cb2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-004i-9000000000-63d6b2cbde40b2bcd6392021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004i-9003000000-0b8ee634478a6f2f0eee2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-000i-0009000000-086098dbff51e692c04f2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0c0r-9850000000-ae199550ba647589f0882021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-004i-9000000000-eab734dd0ed786cbba6d2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-1029000000-37869fd8dcd3ec0f4cc12017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01po-4295000000-7cdbdca2d1d67b21879d2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03fr-9810000000-9b5c3fb12c27e09cf4502017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-002r-4239000000-e56f7b1fecd3064e87832017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004j-9164000000-892445ea4dcd3bf9420d2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9100000000-7c64b90d0daae2c6e5b82017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0009000000-9a74f9cc10019d27995c2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-0149000000-093e852afab8097cfa0f2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03dm-8790000000-0a33128bbe614c27cdf72021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0019000000-345311bd602424b95a492021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
Toxicity Profile
Route of ExposureOral. Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%. The pharmacokinetic profile of the extended release formulation is non linear at 25 mg due to binding of topiramate to carbonic anhydrase in red blood cells. The peak plasma concentration was 24 hours after a single 200 mg oral dose of the extended release formulation. It is also bioequivalent to immediate-release tablet that has been administered twice-daily. Fluctuation of topiramate plasma concentrations at steady-state for Trokendi XR® administered once-daily was approximately 26% and 42% in healthy subjects and in epileptic patients, respectively, compared to approximately 40% and 51%, respectively, for immediate-release topiramate. When topiramate is given to elderly and young adults, the maximum plasma concentration was achieved in 1 to 2 hours.
Mechanism of ToxicityThe precise mechanism of action of topiramate is not known. However, studies have shown that topiramate blocks the action potentials elicited repetitively by a sustained depolarization of the neurons in a time-dependent manner, suggesting a state-dependent sodium channel blocking action. Topiramate also augments the activity of the neurotransmitter gamma-aminobutyrate (GABA) at some subtypes of the GABAA receptor (controls an integral chloride channel), indicating a possible mechanism through potentiation of the activity of GABA. Topiramate also demonstrates antagonism of the AMPA/kainate subtype of the glutamate excitatory amino acid receptor. It also inhibits carbonic anhydrase (particularly isozymes II and IV), but this action is weak and unlikely to be related to its anticonvulsant actions.
MetabolismNot extensively metabolized, 70% of the dose is eliminated unchanged in the urine. The other 30% is metabolized hepatically to six metabolites (formed by hydroxylation, hydrolysis, and glucuronidation), none of which constitute more than 5% of an administered dose. There is evidence of renal tubular reabsorption of topiramate. Route of Elimination: Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). Half Life: 19 to 23 hours. The mean elimination half-life was 31 hours following repeat administration of the extended-release formulation.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. Used to treat epilepsy in children and adults. It is sometimes used as an antidepressant. In children it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is also Food and Drug Administration (FDA) approved for, and most frequently prescribed for, the prevention of migraines. Psychiatrists have used topiramate to treat bipolar disorder,[6] but it is not FDA approved for this purpose. This drug has been investigated for use in treating alcoholism and obesity, especially to reduce binge eating.
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms of overdose include abdominal pain, agitation, blurred vision, convulsions, depression, dizziness, double vision, drowsiness, impaired coordination, impaired mental activity, low blood pressure, reduced consciousness, severe diarrhea, sluggishness, and speech problems.
TreatmentIn acute Topiramate overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of emesis. Activated charcoal has been shown to adsorb topiramate in vitro. Treatment should be appropriately supportive. Hemodialysis is an effective means of removing topiramate from the body. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00273
HMDB IDHMDB05034
PubChem Compound ID5284627
ChEMBL IDCHEMBL220492
ChemSpider ID4447672
KEGG IDC07502
UniProt IDNot Available
OMIM ID
ChEBI ID63631
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTopiramate
PDB IDTOR
ACToR IDNot Available
Wikipedia LinkTopiramate
References
Synthesis Reference

Orn Almarsson, “Topiramate salts and compositions comprising and methods of making and using the same.” U.S. Patent US20040053853, issued March 18, 2004.

MSDSLink
General References
  1. Blum D, Meador K, Biton V, Fakhoury T, Shneker B, Chung S, Mills K, Hammer A, Isojarvi J: Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology. 2006 Aug 8;67(3):400-6. [16894098 ]
  2. Petroff OA, Hyder F, Mattson RH, Rothman DL: Topiramate increases brain GABA, homocarnosine, and pyrrolidinone in patients with epilepsy. Neurology. 1999 Feb;52(3):473-8. [10025774 ]
  3. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
  4. Drugs.com [Link]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. Carbonic anhydrase 2
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.005 uMNot AvailableBindingDB 10887
IC502.1 uMNot AvailableBindingDB 10887
Dissociation0.0138 uMNot AvailableBindingDB 10887
Dissociation0.29 uMNot AvailableBindingDB 10887
References
  1. Maryanoff BE, McComsey DF, Costanzo MJ, Hochman C, Smith-Swintosky V, Shank RP: Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform. J Med Chem. 2005 Mar 24;48(6):1941-7. [15771438 ]
  2. Ma L, Huang YG, Deng YC, Tian JY, Rao ZR, Che HL, Zhang HF, Zhao G: Topiramate reduced sweat secretion and aquaporin-5 expression in sweat glands of mice. Life Sci. 2007 Jun 6;80(26):2461-8. Epub 2007 Apr 29. [17521680 ]
  3. Di Fiore A, Scozzafava A, Winum JY, Montero JL, Pedone C, Supuran CT, De Simone G: Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-sulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1726-31. Epub 2007 Jan 8. [17251017 ]
  4. Casini A, Antel J, Abbate F, Scozzafava A, David S, Waldeck H, Schafer S, Supuran CT: Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg Med Chem Lett. 2003 Mar 10;13(5):841-5. [12617904 ]
  5. Winum JY, Scozzafava A, Montero JL, Supuran CT: Sulfamates and their therapeutic potential. Med Res Rev. 2005 Mar;25(2):186-228. [15478125 ]
  6. Vitale RM, Pedone C, Amodeo P, Antel J, Wurl M, Scozzafava A, Supuran CT, De Simone G: Molecular modeling study for the binding of zonisamide and topiramate to the human mitochondrial carbonic anhydrase isoform VA. Bioorg Med Chem. 2007 Jun 15;15(12):4152-8. Epub 2007 Mar 30. [17420132 ]
  7. Klinger AL, McComsey DF, Smith-Swintosky V, Shank RP, Maryanoff BE: Inhibition of carbonic anhydrase-II by sulfamate and sulfamide groups: an investigation involving direct thermodynamic binding measurements. J Med Chem. 2006 Jun 15;49(12):3496-500. [16759092 ]
  8. Maryanoff BE, McComsey DF, Lee J, Smith-Swintosky VL, Wang Y, Minor LK, Todd MJ: Carbonic anhydrase-II inhibition. what are the true enzyme-inhibitory properties of the sulfamide cognate of topiramate? J Med Chem. 2008 Apr 24;51(8):2518-21. doi: 10.1021/jm7015649. Epub 2008 Mar 26. [18363349 ]
  9. Abbate F, Coetzee A, Casini A, Ciattini S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. Bioorg Med Chem Lett. 2004 Jan 19;14(2):337-41. [14698154 ]
  10. Parker MH, Smith-Swintosky VL, McComsey DF, Huang Y, Brenneman D, Klein B, Malatynska E, White HS, Milewski ME, Herb M, Finley MF, Liu Y, Lubin ML, Qin N, Iannucci R, Leclercq L, Cuyckens F, Reitz AB, Maryanoff BE: Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies. J Med Chem. 2009 Dec 10;52(23):7528-36. doi: 10.1021/jm801432r. [19388676 ]
  11. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [17826101 ]
Target Details
2. Sodium channel protein type 1 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Coppola G, Capovilla G, Montagnini A, Romeo A, Spano M, Tortorella G, Veggiotti P, Viri M, Pascotto A: Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian multicenter open trial. Epilepsy Res. 2002 Mar;49(1):45-8. [11948006 ]
  2. Ceulemans B, Cras P: "Severe myoclonic epilepsy in infancy". Relevance for the clinician of severe epilepsy starting in infancy. Acta Neurol Belg. 2004 Sep;104(3):95-9. [15508261 ]
  3. Ceulemans B, Boel M, Claes L, Dom L, Willekens H, Thiry P, Lagae L: Severe myoclonic epilepsy in infancy: toward an optimal treatment. J Child Neurol. 2004 Jul;19(7):516-21. [15526956 ]
  4. Korff C, Laux L, Kelley K, Goldstein J, Koh S, Nordli D Jr: Dravet syndrome (severe myoclonic epilepsy in infancy): a retrospective study of 16 patients. J Child Neurol. 2007 Feb;22(2):185-94. [17621480 ]
  5. Nieto Barrera M, Candau Fernandez Mensaque R, Nieto Jimenez M: [Severe myoclonic epilepsy in infancy (Dravet's syndrome). Its nosological characteristics and therapeutic aspects]. Rev Neurol. 2003 Jul 1-15;37(1):64-8. [12861512 ]
Target Details
3. Carbonic anhydrase 4
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
References
  1. Abbate F, Casini A, Owa T, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg Med Chem Lett. 2004 Jan 5;14(1):217-23. [14684331 ]
  2. Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. [10768298 ]
  3. Masereel B, Rolin S, Abbate F, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. J Med Chem. 2002 Jan 17;45(2):312-20. [11784136 ]
  4. Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [14971907 ]
Target Details
4. Glutamate receptor ionotropic, kainate 1
General Function:
Voltage-gated cation channel activity
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.
Gene Name:
GRIK1
Uniprot ID:
P39086
Molecular Weight:
103979.665 Da
References
  1. Rogawski MA, Gryder D, Castaneda D, Yonekawa W, Banks MK, Lia H: GluR5 kainate receptors, seizures, and the amygdala. Ann N Y Acad Sci. 2003 Apr;985:150-62. [12724156 ]
  2. Gryder DS, Rogawski MA: Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J Neurosci. 2003 Aug 6;23(18):7069-74. [12904467 ]
  3. Kaminski RM, Banerjee M, Rogawski MA: Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology. 2004 Jun;46(8):1097-104. [15111016 ]
Target Details
5. Carbonic anhydrase 1
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.25 uMNot AvailableBindingDB 10887
References
  1. Abbate F, Coetzee A, Casini A, Ciattini S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. Bioorg Med Chem Lett. 2004 Jan 19;14(2):337-41. [14698154 ]
  2. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [17826101 ]
Target Details
6. Gamma-aminobutyric acid receptor subunit alpha-1
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
7. Carbonic anhydrase 3
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA3
Uniprot ID:
P07451
Molecular Weight:
29557.215 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [17826101 ]
Target Details
8. Carbonic anhydrase 5A, mitochondrial
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Low activity.
Gene Name:
CA5A
Uniprot ID:
P35218
Molecular Weight:
34750.21 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.0254 uMNot AvailableBindingDB 10887
References
  1. Vitale RM, Pedone C, Amodeo P, Antel J, Wurl M, Scozzafava A, Supuran CT, De Simone G: Molecular modeling study for the binding of zonisamide and topiramate to the human mitochondrial carbonic anhydrase isoform VA. Bioorg Med Chem. 2007 Jun 15;15(12):4152-8. Epub 2007 Mar 30. [17420132 ]
9. GABA-A receptor (anion channel) (Protein Group)
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Included Proteins:
P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88