| Record Information |
|---|
| Version |
3.5 |
| Creation Date |
2006-05-18 02:50:34 -0600 |
| Update Date |
2013-02-08 17:13:49 -0700 |
| HMDB ID |
HMDB05034 |
| Secondary Accession Numbers |
None |
| Metabolite Identification |
|---|
| Common Name |
Topiramate |
| 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. |
| Structure |
Download:
MOL |
SDF |
SMILES |
InChI
Display:
2D Structure |
3D Structure
|
| Synonyms |
- Epitomax
- Topamax
- Topamax Sprinkle
- Topiramate
- Topomax
|
| Chemical Formula |
C12H21NO8S |
| Average Molecular Weight |
339.362 |
| Monoisotopic Molecular Weight |
339.098787343 |
| 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 IUPAC Name |
topiramate |
| CAS Registry Number |
97240-79-4 |
| SMILES |
CC1(C)O[C@@H]2CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@H]3[C@@H]2O1 |
| 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 |
KJADKKWYZYXHBB-XBWDGYHZSA-N |
| Chemical Taxonomy |
|---|
| Kingdom |
Organic Compounds |
| Super Class |
Aliphatic Heteropolycyclic Compounds |
| Class |
Dioxolopyrans |
| Sub Class |
N/A |
| Other Descriptors |
- Aliphatic Heteropolycyclic Compounds
- cyclic ketal(ChEBI)
- ketohexose derivative(ChEBI)
- sulfamate ester(ChEBI)
|
| Substituents |
- Acetal
- Meta Dioxolane
- Organic Sulfuric Acid Amide Ester
- Oxane
- Sulfamic Acid Derivative
|
| Direct Parent |
Dioxolopyrans |
| Ontology |
|---|
| Status |
Detected and Quantified |
| Origin |
|
| Biofunction |
Not Available |
| Application |
Not Available |
| Cellular locations |
- Membrane (predicted from logP)
|
| Physical Properties |
|---|
| State |
Solid |
| Experimental Properties |
| Property |
Value |
Reference |
| Melting Point |
125 - 126 °C |
Not Available |
| Boiling Point |
Not Available |
Not Available |
| Water Solubility |
Not Available |
Not Available |
| LogP |
Not Available |
Not Available |
|
| Predicted Properties |
|
| Spectra |
|---|
|
Not Available
|
| Biological Properties |
|---|
| Cellular Locations |
- Membrane (predicted from logP)
|
| Biofluid Locations |
|
| Tissue Location |
|
| Pathways |
Not Available
|
| Normal Concentrations |
|---|
|
| Blood |
Detected and Quantified |
|
1.47 +/- 0.03 uM |
Adult (>18 years old) |
Both |
Normal |
Not Available |
|
| Abnormal Concentrations |
|---|
|
Not Available |
| Associated Disorders and Diseases |
|---|
| Disease References |
None |
| Associated OMIM IDs |
None |
| External Links |
|---|
| DrugBank ID |
Not Available |
| Phenol Explorer Compound ID |
Not Available |
| Phenol Explorer Metabolite ID |
Not Available |
| FoodDB ID |
FDB023601 |
| KNApSAcK ID |
Not Available |
| Chemspider ID |
4447672  |
| KEGG Compound ID |
C07502 |
| BioCyc ID |
Not Available |
| BiGG ID |
Not Available |
| Wikipedia Link |
Topiramate |
| NuGOwiki Link |
HMDB05034 |
| Metagene Link |
HMDB05034 |
| METLIN ID |
Not Available |
| PubChem Compound |
5284627 |
| PDB ID |
TOR |
| ChEBI ID |
63631 |
| References |
|---|
| Synthesis Reference |
Maryanoff, Bruce E.; Gardocki, Joseph F. Anticonvulsant sulfamate derivatives. U.S. (1985), CODEN: USXXAM US 4513006 A 19850423 CAN 103:37701 AN 1985:437701 |
| Material Safety Data Sheet (MSDS) |
Download (PDF)
|
| General References |
- 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.
Pubmed: 10025774
- 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.
Pubmed: 19212411
|
