Repositioning Candidate Details
| Candidate ID: | R0071 |
| Source ID: | DB00273 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Topiramate |
| Synonyms: | |
| Molecular Formula: | C12H21NO8S |
| SMILES: | [H][C@@]12CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@]3([H])[C@]1([H])OC(C)(C)O2 |
| Structure: |
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| DrugBank Description: | Topiramate is a anti-epileptic drug used to manage seizures and prevent migraines.[A175249] It was initially approved by the FDA in 1996. In 2004, topiramate was approved for the prevention of migraine in adults.[A188309,L10544] Since 2012, the extended-release formulation has been approved in combination with [phentermine] for chronic weight management therapy in adults.[L10550] 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.[A175249] Interestingly, topiramate was discovered by chance when attempts were made to formulate a novel antidiabetic drug.[A188330] |
| CAS Number: | 97240-79-4 |
| Molecular Weight: | 339.362 |
| DrugBank 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.[L10544] Topiramate is also used off-label as an adjunct therapy for weight management[L10550] and for mood disorders.[A188312] |
| DrugBank Pharmacology: | Topiramate prevents the occurrence of seizures and prevents migraine symptoms by reducing neural pathway excitability.[A188330,L10544] 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.[L10544] |
| DrugBank MoA: | 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.[L5548] The exact mechanisms by which topiramate exerts pharmacological actions on seizures and migraines are currently not fully characterized.[A188336,L10544] 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.[A175249,L10544] 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.[A175234,T752] By increasing GABA activity and inhibiting glutamate activity, topiramate blocks neuronal excitability, preventing seizures and migraines.[A188333,A188309,L10544] Additionally, it blocks the voltage-dependent sodium channels, further blocking seizure activity.[A175243] Topiramate has been shown to inhibit various carbonic anhydrase isozymes, but the clinical significance of this is unknown at this time.[A10342,A10348,A20066,L10544] |
| Targets: | Gamma-aminobutyric acid receptor subunit alpha-1; Voltage-gated sodium channel alpha subunit; Kainate receptors; Carbonic anhydrase 2; Carbonic anhydrase 4; Voltage gated L-type calcium channel; Carbonic anhydrase 1; Carbonic anhydrase 3; Voltage-dependent R-type calcium channel |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |