Topiramate (CHEM002157)
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| Version | 1.0 | ||||||||
| Creation Date | 2009-07-21 20:26:27 UTC | ||||||||
| Update Date | 2026-05-14 16:25:06 UTC | ||||||||
| Accession Number | CHEM002157 | ||||||||
| Identification | |||||||||
| Common Name | Topiramate | ||||||||
| Class | Small Molecule | ||||||||
| Description | Topiramate 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. | ||||||||
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| Chemical Structure |  | ||||||||
| Synonyms | Not Available | ||||||||
| Chemical Formula | C12H21NO8S | ||||||||
| Average Molecular Mass | 339.362 g/mol | ||||||||
| Monoisotopic Mass | 339.099 g/mol | ||||||||
| CAS Registry Number | 97240-79-4 | ||||||||
| 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 | ||||||||
| Traditional Name | Not Available | ||||||||
| 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 Identifier | 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 | ||||||||
| InChI Key | InChIKey=KJADKKWYZYXHBB-XBWDGYHZSA-N | ||||||||
| Chemical Taxonomy | |||||||||
| Classification | Not classified | ||||||||
| Biological Properties | |||||||||
| Status | Detected and Not Quantified | ||||||||
| Origin | Exogenous | ||||||||
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| Biofluid Locations | Not Available | ||||||||
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| Pathways | Not Available | ||||||||
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| Chemical Roles | Not Available | ||||||||
| Physical Properties | |||||||||
| State | Solid | ||||||||
| Appearance | White powder. | ||||||||
| Experimental Properties |
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| Predicted Properties | Not Available | ||||||||
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| Toxicity Profile | |||||||||
| Route of Exposure | Oral. 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 Toxicity | The 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. | ||||||||
| Metabolism | Not 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 Values | Not Available | ||||||||
| Lethal Dose | Not Available | ||||||||
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). | ||||||||
| Uses/Sources | Used 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 Level | Not Available | ||||||||
| Health Effects | May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. | ||||||||
| Symptoms | Symptoms 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. | ||||||||
| Treatment | In 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) | ||||||||
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| External Links | |||||||||
| Identifiers | Not Available | ||||||||
| 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. | ||||||||
| MSDS | Link | ||||||||
| General References | Not Available | ||||||||
