Explore a selection of our essential drug information below, or:
Identification
- Summary
Topiramate is an anticonvulsant drug used in the control of epilepsy and in the prophylaxis and treatment of migraines.
- Brand Names
- Eprontia, Qsymia, Qudexy, Topamax, Trokendi
- Generic Name
- Topiramate
- DrugBank Accession Number
- DB00273
- Background
Topiramate is a anti-epileptic drug used to manage seizures and prevent migraines.4 It was initially approved by the FDA in 1996. In 2004, topiramate was approved for the prevention of migraine in adults.6,19,23 Since 2012, the extended-release formulation has been approved in combination with phentermine for chronic weight management therapy in adults.21
Characteristics that distinguish topiramate from other antiepileptic drugs are a monosaccharide chemical structure containing a sulfamate, and 40% of its mass accounted for by oxygen.4 Interestingly, topiramate was discovered by chance when attempts were made to formulate a novel antidiabetic drug.8
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Topiramate (DB00273)
- Weight
- Average: 339.362
Monoisotopic: 339.098787343 - Chemical Formula
- C12H21NO8S
- Synonyms
- 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate
- 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose sulfamate
- Tipiramate
- Tipiramato
- Topiramate
- Topiramato
- Topiramatum
- TPM
- External IDs
- MCN-4853
- RWJ-17021
- RWJ-17021-000
- USL-255
- USL255
Pharmacology
- Indication
Topiramate is indicated for the following conditions: 1)Monotherapy for partial onset or primary generalized tonic-clonic seizures for patients 2 years of age and above 2)Adjunctive therapy for partial onset seizures or primary generalized tonic-clonic seizures for both adult and pediatric patients above 2 years old 3)Adjunctive therapy for seizures associated with Lennox-Gastaut syndrome in patients above 2 years of age 4)Prophylaxis of migraine in children 12 years of age and older and adults.19
Topiramate is also used off-label as an adjunct therapy for weight management21 and for mood disorders.7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Alcohol dependence ••• ••••• •••••• Adjunct therapy in management of Epilepsy, primary generalized tonic-clonic seizures •••••••••••• •••••••• •••••••• ••••••• Management of Epilepsy, primary generalized tonic-clonic seizures •••••••••••• •••••••• •••••••• ••••••• Adjunct therapy in management of Lennox-gastaut syndrome •••••••••••• •••••••• ••••••••• •••••• Prophylaxis of Migraine •••••••••••• •••••••• •••••••• ••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Topiramate prevents the occurrence of seizures and prevents migraine symptoms by reducing neural pathway excitability.8,19 It is important to note that this drug may cause metabolic acidosis, mood changes, suicidal thoughts and attempts, as well as kidney stones. When topiramate is combined with valproic acid, it is known to cause hypothermia.19
- Mechanism of action
A seizure is an abnormal and unregulated electrical discharge occurring in the brain. This leads to transient interruption in brain function, manifested by reduced alertness, abnormal sensations, and focal involuntary movements or convulsions. Several types of seizures exist, with common types including tonic-clonic seizures and partial onset seizures.17
The exact mechanisms by which topiramate exerts pharmacological actions on seizures and migraines are currently not fully characterized.10,19 Several properties of this drug, however, are likely to contribute to its therapeutic effects. Topiramate has been observed to exert actions on voltage-dependent sodium channels, GABA receptors, and glutamate receptors.4,19
Topiramate stimulates GABA-A receptor activity at brain non-benzodiazepine receptor sites and reduces glutamate activity at both AMPA and kainate receptors. Normally, GABA-A receptors are inhibitory and glutaminergic receptors are stimulatory for neuronal activity.15,16 By increasing GABA activity and inhibiting glutamate activity, topiramate blocks neuronal excitability, preventing seizures and migraines.9,6,19 Additionally, it blocks the voltage-dependent sodium channels, further blocking seizure activity.15 Topiramate has been shown to inhibit various carbonic anhydrase isozymes, but the clinical significance of this is unknown at this time.11,12,13,19
Target Actions Organism AGlutamate receptor ionotropic, kainate 1 antagonistHumans AGamma-aminobutyric acid receptor subunit alpha-1 agonistHumans AVoltage-gated sodium channel alpha subunit inhibitorHumans AKainate receptors antagonistHumans ACarbonic anhydrase 2 inhibitorHumans ACarbonic anhydrase 4 inhibitorHumans AVoltage gated L-type calcium channel antagonistHumans UCarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 3 inhibitorHumans UVoltage-dependent R-type calcium channel antagonistHumans - Absorption
After a 400mg dose in one clinical trial, topiramate reached maximal concentrations within 1.8-4.3 hours and ranged from 1.73-28.7 ug/mL. Food did not significantly affect the extent of absorption, despite delaying time to peak concentration. In patients with normal creatinine clearance, steady state concentrations are reached within 4 days.3 The bioavailability of topiramate in tablet form is about 80% compared to a topiramate solution.19
- Volume of distribution
The mean apparent volume of distribution of topiramate ranges from 0.6-0.8 L/kg when doses of 100mg to 1200mg are given.3 Topiramate readily crosses the blood-brain barrier.4
- Protein binding
Topiramate is not highly bound to plasma proteins, with an estimated plasma protein binding of 9-17% according to some studies.3,4 The FDA label indicates that the protein binding of topiramate is 15-41%.19
- Metabolism
The metabolites of topiramate are not known to be active.2 The metabolism of topiramate is characterized by reactions of glucuronidation, hydroxylation and hydrolysis that lead to the production of six minor metabolites.19 Some of topiramate's metabolites include 2,3-desisopropylidene topiramate, 4,5-desisopropylidene topiramate, 9-hydroxy topiramate, and 10-hydroxy topiramate.14
Hover over products below to view reaction partners
- Route of elimination
Topiramate is mainly eliminated through the kidneys.15 About 70-80% of the eliminated dose is found unchanged in the urine.3,19
- Half-life
The elimination half-life is reported to be in the range of 19-23 hours.3 If topiramate is given with enzyme-inducers, the half-life can be reduced to 12-15 hours because of increased metabolism.3
- Clearance
The mean oral plasma clearance of topiramate ranges from 22-36 mL/min while the renal clearance is 17-18 mL/min, according to one pharmacokinetic study.3 The FDA label for topiramate indicates a similar oral plasma clearance of approximately 20 to 30 mL/min in adults.19
- Adverse Effects
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The LD50 of intraperitoneal topiramate in the rat is above 1500 mg/kg.20
Overdose information
In a study of 4 healthy adult women taking topiramate, the severity of clinical effects following an overdose ranged from asymptomatic to severe, with no deaths reported.5 According to the FDA prescribing information for topiramate, an overdose may cause hypotension, severe metabolic acidosis, coma, abdominal pain, visual disturbances, convulsions, drowsiness, speech abnormalities, impaired mentation and coordination, stupor, agitation, dizziness, as well as depression.19
In the case of a recent ingestion of topiramate, the stomach contents should be emptied through the induction of emesis or gastric lavage. Offer supportive treatment, including activated charcoal and hemodialysis.19
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Topiramate is combined with 1,2-Benzodiazepine. Abacavir Topiramate may decrease the excretion rate of Abacavir which could result in a higher serum level. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Topiramate. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Topiramate. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Topiramate. - Food Interactions
- Avoid a ketogenic diet. This type of diet increases the risk of kidney stones.
- Take with or without food. Food slightly alters absorption but not to any clinically significant extent.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Topiramate calcium P956SY6RA6 1246279-00-4 VNRLRDKZOMPUAG-RZTSBURASA-N Topiramate potassium SMU8E1YBZ3 488127-51-1 VEKVPJSPZRTTGR-WGAVTJJLSA-N Topiramate sodium N808MSN0PT 488127-49-7 ZUWVVMMRNQEJMW-WGAVTJJLSA-N - Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eprontia Solution 25 mg/1mL Oral Azurity Pharmaceuticals, Inc. 2021-12-06 Not applicable US 
Gln-topiramate Tablet 100 mg Oral Glenmark Pharmaceuticals Inc., USA Not applicable Not applicable Canada 
Gln-topiramate Tablet 25 mg Oral Glenmark Pharmaceuticals Inc., USA 2007-07-12 Not applicable Canada Gln-topiramate Tablet 200 mg Oral Glenmark Pharmaceuticals Inc., USA 2007-07-12 Not applicable Canada Gln-topiramate Tablet 25 mg Oral Glenmark Pharmaceuticals Inc., USA Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Abbott-topiramate Tablet 25 mg Oral Bgp Pharma Ulc 2014-03-12 2015-12-31 Canada Abbott-topiramate Tablet 200 mg Oral Bgp Pharma Ulc 2014-03-17 2015-12-31 Canada Abbott-topiramate Tablet 100 mg Oral Bgp Pharma Ulc 2014-03-12 2015-12-31 Canada Accel-topiramate Tablet 25 mg Oral Accel Pharma Inc 2015-03-26 2017-01-27 Canada Accel-topiramate Tablet 200 mg Oral Accel Pharma Inc 2015-03-26 2017-01-27 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Qsymia Topiramate (46 mg/1) + Phentermine hydrochloride (7.5 mg/1) Capsule, extended release Oral VIVUS LLC 2012-09-17 Not applicable US Qsymia Topiramate (23 mg/1) + Phentermine hydrochloride (3.75 mg/1) Capsule, extended release Oral VIVUS LLC 2012-09-17 Not applicable US Qsymia Topiramate (69 mg/1) + Phentermine hydrochloride (11.25 mg/1) Capsule, extended release Oral VIVUS LLC 2012-09-17 Not applicable US Qsymia Topiramate (92 mg/1) + Phentermine hydrochloride (15 mg/1) Capsule, extended release Oral VIVUS LLC 2012-09-17 Not applicable US
Categories
- ATC Codes
- A08AA51 — Phentermine and topiramate
- A08AA — Centrally acting antiobesity products
- A08A — ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
- A08 — ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Alimentary Tract and Metabolism
- Anti-Obesity Agents
- Anticonvulsants
- Antiobesity Preparations, Excl. Diet Products
- Carbohydrates
- Central Nervous System Agents
- Central Nervous System Depressants
- Centrally Acting Antiobesity Products
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Decreased Central Nervous System Disorganized Electrical Activity
- Drugs that are Mainly Renally Excreted
- Enzyme Inducing Antiepileptic Drugs
- Hexoses
- Ketoses
- Miscellaneous Anticonvulsants
- Monosaccharides
- Nervous System
- Neuroprotective Agents
- P-glycoprotein substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dioxolopyrans. These are compounds containing a dioxolopyran moiety, which consists of a dioxole ring fused to a pyran ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Dioxolopyrans
- Sub Class
- Not Available
- Direct Parent
- Dioxolopyrans
- Alternative Parents
- Ketals / Oxanes / Monosaccharides / Organic sulfuric acids and derivatives / 1,3-dioxolanes / Oxacyclic compounds / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives
- Substituents
- Acetal / Aliphatic heteropolycyclic compound / Dioxolopyran / Hydrocarbon derivative / Ketal / Meta-dioxolane / Monosaccharide / Organic nitrogen compound / Organic oxide / Organic oxygen compound
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- cyclic ketal, sulfamate ester, ketohexose derivative (CHEBI:63631)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0H73WJJ391
- CAS number
- 97240-79-4
- InChI Key
- KJADKKWYZYXHBB-XBWDGYHZSA-N
- InChI
- InChI=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
- IUPAC Name
- [(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0^{2,6}]dodecan-6-yl]methyl sulfamate
- SMILES
- [H][C@@]12CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@]3([H])[C@]1([H])OC(C)(C)O2
References
- Synthesis Reference
Geza Arvai, Sandor Garaczi, Attila Mate, Ferenc Lukacs, Zsolt Viski, Geza Schneider.(2004).US20060040874A1.Retrieved from: https://patents.google.com/patent/US20060040874A1/en.
US20040053853- General References
- Ford L, Goldberg JL, Selan F, Greenberg HE, Shi Y: Comprehensive review of visual defects reported with topiramate. Clin Ophthalmol. 2017 May 23;11:983-992. doi: 10.2147/OPTH.S125768. eCollection 2017. [Article]
- Brigo F, Bragazzi NL, Igwe SC, Nardone R, Trinka E: Topiramate in the Treatment of Generalized Convulsive Status Epilepticus in Adults: A Systematic Review with Individual Patient Data Analysis. Drugs. 2017 Jan;77(1):67-74. doi: 10.1007/s40265-016-0672-2. [Article]
- Garnett WR: Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41 Suppl 1:S61-5. [Article]
- Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE: An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41 Suppl 1:S3-9. [Article]
- Wisniewski M, Lukasik-Glebocka M, Anand JS: Acute topiramate overdose--clinical manifestations. Clin Toxicol (Phila). 2009 Apr;47(4):317-20. doi: 10.1080/15563650601117954. [Article]
- Wenzel RG, Schwarz K, Padiyara RS: Topiramate for migraine prevention. Pharmacotherapy. 2006 Mar;26(3):375-87. doi: 10.1592/phco.26.3.375. [Article]
- Arnone D: Review of the use of Topiramate for treatment of psychiatric disorders. Ann Gen Psychiatry. 2005 Feb 16;4(1):5. doi: 10.1186/1744-859X-4-5. [Article]
- Maryanoff BE: Sugar sulfamates for seizure control: discovery and development of topiramate, a structurally unique antiepileptic drug. Curr Top Med Chem. 2009;9(11):1049-62. doi: 10.2174/156802609789630938. [Article]
- Chung JY, Kim MW, Kim M: Efficacy of zonisamide in migraineurs with nonresponse to topiramate. Biomed Res Int. 2014;2014:891348. doi: 10.1155/2014/891348. Epub 2014 Jul 2. [Article]
- Naegel S, Obermann M: Topiramate in the prevention and treatment of migraine: efficacy, safety and patient preference. Neuropsychiatr Dis Treat. 2010 Feb 3;6:17-28. doi: 10.2147/ndt.s6459. [Article]
- 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. [Article]
- Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. doi: 10.1111/j.1528-1157.2000.tb06047.x. [Article]
- 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. [Article]
- Caldwell GW, Wu WN, Masucci JA, McKown LA, Gauthier D, Jones WJ, Leo GC, Maryanoff BE: Metabolism and excretion of the antiepileptic/antimigraine drug, Topiramate in animals and humans. Eur J Drug Metab Pharmacokinet. 2005 Jul-Sep;30(3):151-64. doi: 10.1007/BF03190614. [Article]
- Walker MC, Sander JW: Topiramate: a new antiepileptic drug for refractory epilepsy. Seizure. 1996 Sep;5(3):199-203. [Article]
- Mary J. Allen; Sandeep Sharma (2019). GABA receptor. StatPearls.
- Merck [Link]
- Topamax, manufacturer's website [Link]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
- MSDS, Topiramate [Link]
- Qsymia approval information [Link]
- FDA Approved Drug Products: Qsymia (phentermine and topiramate), extended-release capsules for oral use [Link]
- FDA Approved Drug Products: TROKENDI XR (topiramate) extended-release capsules for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0005034
- KEGG Drug
- D00537
- KEGG Compound
- C07502
- PubChem Compound
- 5284627
- PubChem Substance
- 46508334
- ChemSpider
- 4447672
- BindingDB
- 10887
- 38404
- ChEBI
- 63631
- ChEMBL
- CHEMBL220492
- ZINC
- ZINC000095616603
- Therapeutic Targets Database
- DAP000137
- PharmGKB
- PA451728
- PDBe Ligand
- TOR
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Topiramate
- PDB Entries
- 3hku / 3lxe / 5jna / 7yg5
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Arthritis / Gout Flares / Headache / Migraine / Muscle Spasms / Radicular syndrome / Synovitis / Tendonitis 1 somestatus stop reason just information to hide Not Available Completed Not Available Convulsions / Epilepsy / Osteopenia (Disorder) / Osteoporosis / Seizures 1 somestatus stop reason just information to hide Not Available Completed Not Available Epilepsy 2 somestatus stop reason just information to hide Not Available Completed Not Available Epilepsy / Seizures 1 somestatus stop reason just information to hide Not Available Completed Not Available Epileptic seizure 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Ortho mcneil janssen pharmaceuticals inc
- Barr laboratories inc
- Mylan pharmaceuticals inc
- Sandoz inc
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Zydus pharmaceuticals usa inc
- Accord healthcare inc
- Apotex inc etobicoke site
- Aurobindo pharma ltd
- Cipla ltd
- Glenmark generics ltd
- Invagen pharmaceuticals inc
- Pliva hrvatska doo
- Ranbaxy laboratories ltd
- Roxane laboratories inc
- Sun pharmaceutical industries ltd
- Torrent pharmaceuticals ltd
- Unichem laboratories ltd
- Upsher smith laboratories inc
- Packagers
- Amerisource Health Services Corp.
- Apotex Inc.
- A-S Medication Solutions LLC
- Atlantic Biologicals Corporation
- Aurobindo Pharma Ltd.
- Avkare Incorporated
- Barr Pharmaceuticals
- Blenheim Pharmacal
- Bryant Ranch Prepack
- Cadila Healthcare Ltd.
- Camber Pharmaceuticals Inc.
- Cardinal Health
- Cipla Ltd.
- Cobalt Pharmaceuticals Inc.
- Comprehensive Consultant Services Inc.
- DAVA Pharmaceuticals
- Dept Health Central Pharmacy
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Ethypharm
- Gallipot
- Glenmark Generics Ltd.
- Greenstone LLC
- Heartland Repack Services LLC
- Innoviant Pharmacy Inc.
- InvaGen Pharmaceuticals Inc.
- Janssen-Ortho Inc.
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Major Pharmaceuticals
- McNeil Laboratories
- Medisca Inc.
- Mylan
- Nucare Pharmaceuticals Inc.
- Ortho Mcneil Janssen Pharmaceutical Inc.
- PD-Rx Pharmaceuticals Inc.
- Pharmacy Service Center
- Physicians Total Care Inc.
- Pliva Inc.
- Prepak Systems Inc.
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Sandoz
- Shanghai Junjie Biotechnology Co. Ltd.
- Southwood Pharmaceuticals
- Stat Rx Usa
- Sun Pharmaceutical Industries Ltd.
- Teva Pharmaceutical Industries Ltd.
- Torrent Pharmaceuticals
- UDL Laboratories
- Unichem Laboratories Ltd.
- Upsher Smith Laboratories
- Vangard Labs Inc.
- Zydus Pharmaceuticals
- Dosage Forms
Form Route Strength Tablet Oral 100.0000 mg Tablet, film coated Oral Solution Oral 25 mg/1mL Capsule Oral 5.000 mg Tablet Oral 100.000 mg Tablet, film coated Oral 100 mg Tablet, film coated Oral 25 mg Tablet Oral 50 mg Capsule, extended release Oral Capsule, extended release Oral 150 mg/1 Capsule, extended release Oral 200 mg/1 Tablet Oral 200 1/1 Tablet Oral 25 meq/1 Tablet, film coated Oral 20 mg Tablet Oral 400 mg Capsule, coated Oral 50 mg Capsule, coated Oral 15 mg Capsule, coated Oral 25 mg Capsule Oral 15 mg Capsule, coated pellets Oral 15 mg/1 Capsule, coated pellets Oral 25 mg/1 Capsule, gelatin coated Oral 15 mg Capsule, gelatin coated Oral 25 mg Capsule, gelatin coated Oral 50 mg Tablet Oral 50.000 mg Tablet, film coated Oral 300 MG Tablet, film coated Oral 400 MG Tablet Oral 100 mg Capsule, coated pellets Oral 15 mg Tablet Oral 200 mg Capsule, coated pellets Oral 25 mg Tablet Oral 25 mg Capsule, coated pellets Oral 50 mg Tablet, coated Oral 100 mg/1 Tablet, coated Oral 200 mg/1 Tablet, coated Oral 25 mg/1 Tablet, coated Oral 50 mg/1 Tablet, film coated Oral 200 mg Tablet, film coated Oral 50 mg Capsule Oral 15 mg/1 Capsule Oral 25 mg/1 Capsule, extended release Oral 100 mg/1 Capsule, extended release Oral 25 mg/1 Capsule, extended release Oral 50 mg/1 Powder Not applicable 1 1/1kg Tablet Oral 100 mg/1 Tablet Oral 200 mg/1 Tablet Oral 25 mg/1 Tablet Oral 50 mg/1 Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 200 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 50 mg/1 Capsule Oral Tablet, film coated Oral 100.0 mg Tablet Oral 25.000 mg Tablet, coated Oral 100 mg Tablet, coated Oral 25 mg Tablet, coated Oral 50 mg Capsule Oral 25 mg Capsule Oral 50 mg - Prices
Unit description Cost Unit Topiramate 200 mg tablet 8.32USD tablet Topamax 200 mg tablet 7.68USD tablet Topiramate 100 mg tablet 7.11USD tablet Topamax 100 mg tablet 6.31USD tablet Topamax 50 mg tablet 5.96USD tablet Topiramate 50 mg tablet 5.21USD tablet Topiramate 25 mg Sprinkle Capsule 3.04USD capsule Topiramate 25 mg tablet 2.61USD tablet Topiramate 99.7% powder 2.59USD g Topiramate 15 mg Sprinkle Capsule 2.52USD capsule Topamax 25 mg tablet 2.46USD tablet Co Topiramate 200 mg Tablet 2.08USD tablet Mylan-Topiramate 200 mg Tablet 2.08USD tablet Novo-Topiramate 200 mg Tablet 2.08USD tablet Phl-Topiramate 200 mg Tablet 2.08USD tablet Pms-Topiramate 200 mg Tablet 2.08USD tablet Ratio-Topiramate 200 mg Tablet 2.08USD tablet Sandoz Topiramate 200 mg Tablet 2.08USD tablet Topamax Sprinkle 25 mg Capsule 1.35USD capsule Sandoz Topiramate 100 mg Tablet 1.31USD tablet Co Topiramate 100 mg Tablet 1.31USD tablet Mylan-Topiramate 100 mg Tablet 1.31USD tablet Novo-Topiramate 100 mg Tablet 1.31USD tablet Phl-Topiramate 100 mg Tablet 1.31USD tablet Pms-Topiramate 100 mg Tablet 1.31USD tablet Ratio-Topiramate 100 mg Tablet 1.31USD tablet Topamax Sprinkle 15 mg Capsule 1.29USD capsule Pms-Topiramate 50 mg Tablet 1.05USD tablet Co Topiramate 25 mg Tablet 0.69USD tablet Mylan-Topiramate 25 mg Tablet 0.69USD tablet Novo-Topiramate 25 mg Tablet 0.69USD tablet Phl-Topiramate 25 mg Tablet 0.69USD tablet Pms-Topiramate 25 mg Tablet 0.69USD tablet Ratio-Topiramate 25 mg Tablet 0.69USD tablet Sandoz Topiramate 25 mg Tablet 0.69USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2322644 No 2005-07-26 2019-03-01 Canada US5998380 Yes 1999-12-07 2016-04-13 US US6503884 Yes 2003-01-07 2016-04-13 US US7018983 Yes 2006-03-28 2016-04-13 US US7498311 Yes 2009-03-03 2016-04-13 US US7125560 Yes 2006-10-24 2019-09-01 US US6071537 No 2000-06-06 2017-06-23 US US8895057 No 2014-11-25 2028-06-09 US US7056890 No 2006-06-06 2020-06-14 US US7553818 No 2009-06-30 2020-06-14 US US7659256 No 2010-02-09 2020-06-14 US US7674776 No 2010-03-09 2020-06-14 US US8580299 No 2013-11-12 2029-06-14 US US9011906 No 2015-04-21 2028-06-09 US US9011905 No 2015-04-21 2028-06-09 US US8895058 No 2014-11-25 2028-06-09 US US8580298 No 2013-11-12 2029-05-15 US US9101545 No 2015-08-11 2033-03-19 US US8652527 No 2014-02-18 2033-03-19 US US8889190 No 2014-11-18 2033-03-19 US US8889191 No 2014-11-18 2027-11-16 US US8298580 No 2012-10-30 2027-11-16 US US8663683 No 2014-03-04 2027-11-16 US US8877248 No 2014-11-04 2027-11-16 US US8298576 No 2012-10-30 2028-04-04 US US8992989 No 2015-03-31 2027-11-16 US US9555005 No 2017-01-31 2033-03-19 US US9549940 No 2017-01-24 2027-11-16 US US9555004 No 2017-01-31 2027-11-16 US US9622983 No 2017-04-18 2027-11-16 US US10314790 No 2019-06-11 2027-11-16 US US10363224 No 2019-07-30 2033-03-19 US US11433046 No 2020-08-21 2040-08-21 US US11633374 No 2020-08-21 2040-08-21 US US11826343 No 2020-08-21 2040-08-21 US US11911362 No 2020-08-21 2040-08-21 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 123-125 ºC https://www.chemicalbook.com/ChemicalProductProperty_US_CB7402630.aspx boiling point (°C) 438.7 https://www.lookchem.com/Topiramate/ water solubility 9.8 mg/mL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020505s038s039,020844s032s034lbl.pdf logP 0.13 http://foodb.ca/compounds/FDB023601 logS -1.7 http://foodb.ca/compounds/FDB023601 pKa 8.7 http://foodb.ca/compounds/FDB023601 - Predicted Properties
Property Value Source Water Solubility 6.8 mg/mL ALOGPS logP 1.29 ALOGPS logP 0.13 Chemaxon logS -1.7 ALOGPS pKa (Strongest Acidic) 11.09 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 115.54 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 72.3 m3·mol-1 Chemaxon Polarizability 32.4 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9955 Blood Brain Barrier + 0.9382 Caco-2 permeable - 0.6055 P-glycoprotein substrate Non-substrate 0.7905 P-glycoprotein inhibitor I Non-inhibitor 0.5311 P-glycoprotein inhibitor II Non-inhibitor 0.9479 Renal organic cation transporter Non-inhibitor 0.9131 CYP450 2C9 substrate Non-substrate 0.9479 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.542 CYP450 1A2 substrate Non-inhibitor 0.6623 CYP450 2C9 inhibitor Non-inhibitor 0.7259 CYP450 2D6 inhibitor Non-inhibitor 0.8674 CYP450 2C19 inhibitor Non-inhibitor 0.6539 CYP450 3A4 inhibitor Non-inhibitor 0.8469 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7952 Ames test AMES toxic 0.518 Carcinogenicity Non-carcinogens 0.5578 Biodegradation Not ready biodegradable 0.9803 Rat acute toxicity 2.5682 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8882 hERG inhibition (predictor II) Non-inhibitor 0.8734
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 177.8899278 predictedDarkChem Lite v0.1.0 [M-H]- 179.0720278 predictedDarkChem Lite v0.1.0 [M-H]- 180.0506278 predictedDarkChem Lite v0.1.0 [M-H]- 180.4344 predictedDeepCCS 1.0 (2019) [M+H]+ 179.0413278 predictedDarkChem Lite v0.1.0 [M+H]+ 179.5417278 predictedDarkChem Lite v0.1.0 [M+H]+ 179.8334278 predictedDarkChem Lite v0.1.0 [M+H]+ 183.69444 predictedDeepCCS 1.0 (2019) [M+Na]+ 178.0815278 predictedDarkChem Lite v0.1.0 [M+Na]+ 180.0533278 predictedDarkChem Lite v0.1.0 [M+Na]+ 191.19173 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. 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
- Specific Function
- glutamate-gated calcium ion channel activity
- Gene Name
- GRIK1
- Uniprot ID
- P39086
- Uniprot Name
- Glutamate receptor ionotropic, kainate 1
- Molecular Weight
- 103979.665 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, PubMed:30602789). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity)
- Specific Function
- GABA-A receptor activity
- Gene Name
- GABRA1
- Uniprot ID
- P14867
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-1
- Molecular Weight
- 51801.395 Da
References
- Garnett WR: Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41 Suppl 1:S61-5. [Article]
- Chung JY, Kim MW, Kim M: Efficacy of zonisamide in migraineurs with nonresponse to topiramate. Biomed Res Int. 2014;2014:891348. doi: 10.1155/2014/891348. Epub 2014 Jul 2. [Article]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 (PubMed:14672992). Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons. Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli
- Specific Function
- voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
Components:
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. 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
- Specific Function
- glutamate-gated calcium ion channel activity
Components:
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Braga MF, Aroniadou-Anderjaska V, Li H, Rogawski MA: Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons. J Pharmacol Exp Ther. 2009 Aug;330(2):558-66. doi: 10.1124/jpet.109.153908. Epub 2009 May 5. [Article]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the reversible hydration of carbon dioxide (PubMed:11327835, PubMed:11802772, PubMed:11831900, PubMed:12056894, PubMed:12171926, PubMed:1336460, PubMed:14736236, PubMed:15300855, PubMed:15453828, PubMed:15667203, PubMed:15865431, PubMed:16106378, PubMed:16214338, PubMed:16290146, PubMed:16686544, PubMed:16759856, PubMed:16807956, PubMed:17127057, PubMed:17251017, PubMed:17314045, PubMed:17330962, PubMed:17346964, PubMed:17540563, PubMed:17588751, PubMed:17705204, PubMed:18024029, PubMed:18162396, PubMed:18266323, PubMed:18374572, PubMed:18481843, PubMed:18618712, PubMed:18640037, PubMed:18942852, PubMed:1909891, PubMed:1910042, PubMed:19170619, PubMed:19186056, PubMed:19206230, PubMed:19520834, PubMed:19778001, PubMed:7761440, PubMed:7901850, PubMed:8218160, PubMed:8262987, PubMed:8399159, PubMed:8451242, PubMed:8485129, PubMed:8639494, PubMed:9265618, PubMed:9398308). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). 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
- Specific Function
- arylesterase activity
- Gene Name
- CA2
- Uniprot ID
- P00918
- Uniprot Name
- Carbonic anhydrase 2
- Molecular Weight
- 29245.895 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Winum JY, Scozzafava A, Montero JL, Supuran CT: Sulfamates and their therapeutic potential. Med Res Rev. 2005 Mar;25(2):186-228. [Article]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH (PubMed:15563508, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17652713, PubMed:17705204, PubMed:18618712, PubMed:19186056, PubMed:19206230, PubMed:7625839). May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis (PubMed:15563508). It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid (PubMed:15563508)
- Specific Function
- carbonate dehydratase activity
- Gene Name
- CA4
- Uniprot ID
- P22748
- Uniprot Name
- Carbonic anhydrase 4
- Molecular Weight
- 35032.075 Da
References
- 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. [Article]
- Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. doi: 10.1111/j.1528-1157.2000.tb06047.x. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
- Specific Function
- alpha-actinin binding
Components:
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Catalyzes the reversible hydration of carbon dioxide (PubMed:10550681, PubMed:16506782, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17407288, PubMed:18618712, PubMed:19186056, PubMed:19206230). Can hydrate cyanamide to urea (PubMed:10550681)
- Specific Function
- arylesterase activity
- Gene Name
- CA1
- Uniprot ID
- P00915
- Uniprot Name
- Carbonic anhydrase 1
- Molecular Weight
- 28870.0 Da
References
- 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. [Article]
- Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. doi: 10.1111/j.1528-1157.2000.tb06047.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Reversible hydration of carbon dioxide
- Specific Function
- carbonate dehydratase activity
- Gene Name
- CA3
- Uniprot ID
- P07451
- Uniprot Name
- Carbonic anhydrase 3
- Molecular Weight
- 29557.215 Da
References
- 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. [Article]
- Lehmann WD, Neumann GK, Kessler KF, Jonatha WD: [Frequency of obstetrical operations and perinatal mortality before and after admission of continuous fetal monitoring (author's transl)]. Geburtshilfe Frauenheilkd. 1976 Mar;36(3):247-55. [Article]
- Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. doi: 10.1111/j.1528-1157.2000.tb06047.x. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells (PubMed:30343943). They are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. R-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by nickel. They are however insensitive to dihydropyridines (DHP). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing
- Specific Function
- calcium ion binding
Components:
References
- Wormuth C, Lundt A, Henseler C, Muller R, Broich K, Papazoglou A, Weiergraber M: Review: Cav2.3 R-type Voltage-Gated Ca(2+) Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity. Open Neurol J. 2016 Sep 30;10:99-126. doi: 10.2174/1874205X01610010099. eCollection 2016. [Article]
- Kuzmiski JB, Barr W, Zamponi GW, MacVicar BA: Topiramate inhibits the initiation of plateau potentials in CA1 neurons by depressing R-type calcium channels. Epilepsia. 2005 Apr;46(4):481-9. doi: 10.1111/j.0013-9580.2005.35304.x. [Article]
- Maryanoff BE: Phenotypic Assessment and the Discovery of Topiramate. ACS Med Chem Lett. 2016 Jun 13;7(7):662-5. doi: 10.1021/acsmedchemlett.6b00176. eCollection 2016 Jul 14. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Nallani SC, Glauser TA, Hariparsad N, Setchell K, Buckley DJ, Buckley AR, Desai PB: Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate. Epilepsia. 2003 Dec;44(12):1521-8. [Article]
- Benedetti MS: Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):301-19. doi: 10.1111/j.1472-8206.2000.tb00411.x. [Article]
- Topamax (Topiramate) FDA Label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Garnett WR: Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41 Suppl 1:S61-5. [Article]
- Sachdeo RC, Sachdeo SK, Levy RH, Streeter AJ, Bishop FE, Kunze KL, Mather GG, Roskos LK, Shen DD, Thummel KE, Trager WF, Curtin CR, Doose DR, Gisclon LG, Bialer M: Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Epilepsia. 2002 Jul;43(7):691-6. [Article]
- Flockhart Table of Drug Interactions [Link]
- FDA Approved Drug Products: Topamax (topiramate) for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- Curator comments
- Although topiramate binds to serum albumin, it is not highly bound.
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Luna-Tortos C, Rambeck B, Jurgens UH, Loscher W: The antiepileptic drug topiramate is a substrate for human P-glycoprotein but not multidrug resistance proteins. Pharm Res. 2009 Nov;26(11):2464-70. doi: 10.1007/s11095-009-9961-8. [Article]
- Sills GJ, Kwan P, Butler E, de Lange EC, van den Berg DJ, Brodie MJ: P-glycoprotein-mediated efflux of antiepileptic drugs: preliminary studies in mdr1a knockout mice. Epilepsy Behav. 2002 Oct;3(5):427-432. doi: 10.1016/s1525-5050(02)00511-5. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943)
- Specific Function
- [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
Components:
References
- Ha E, Yim SV, Jung KH, Yoon SH, Zheng LT, Kim MJ, Hong SJ, Choe BK, Baik HH, Chung JH, Kim JW: Topiramate stimulates glucose transport through AMP-activated protein kinase-mediated pathway in L6 skeletal muscle cells. Pharmacogenomics J. 2006 Sep-Oct;6(5):327-32. doi: 10.1038/sj.tpj.6500366. Epub 2006 Jan 17. [Article]
- Wilkes JJ, Nguyen MT, Bandyopadhyay GK, Nelson E, Olefsky JM: Topiramate treatment causes skeletal muscle insulin sensitization and increased Acrp30 secretion in high-fat-fed male Wistar rats. Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E1015-22. doi: 10.1152/ajpendo.00169.2005. Epub 2005 Jul 19. [Article]
- Coomans CP, Geerling JJ, van den Berg SA, van Diepen HC, Garcia-Tardon N, Thomas A, Schroder-van der Elst JP, Ouwens DM, Pijl H, Rensen PC, Havekes LM, Guigas B, Romijn JA: The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system. Br J Pharmacol. 2013 Oct;170(4):908-18. doi: 10.1111/bph.12338. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 08:50