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Details

Stereochemistry ABSOLUTE
Molecular Formula C12H21NO8S
Molecular Weight 339.362
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TOPIRAMATE

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

InChIKey=KJADKKWYZYXHBB-XBWDGYHZSA-N
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

HIDE SMILES / InChI

Molecular Formula C12H21NO8S
Molecular Weight 339.362
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. 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, particular 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 secundarily generalized tonic-clonic seizures in the kindling model, findings predective of a broad spectrum of antiseizure activities clinically. 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 GABAAreceptor (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. Topiramate is used for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. In children it is also used for treatment of Lennox-Gastaut syndrome. Topiramate is sold under the brand name Topamax. A combination product containing phentermine and topiramate extended-release called QSYMIA® is indicated for the management of obesity.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
5.0 nM [Ki]
4.9 µM [Ki]
0.9 nM [Ki]
3.8 nM [Ki]
63.0 nM [Ki]
30.0 nM [Ki]
47.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TOPAMAX
Preventing
TOPAMAX

Cmax

ValueDoseCo-administeredAnalytePopulation
1.63 μg/mL
100 mg single, oral
TOPIRAMATE plasma
Homo sapiens
1.46 μg/mL
100 mg single, oral
TOPIRAMATE plasma
Homo sapiens
8 μg/mL
400 mg single, oral
TOPIRAMATE plasma
Homo sapiens
6.98 μg/mL
400 mg single, oral
TOPIRAMATE plasma
Homo sapiens
3.68 μg/mL
200 mg single, oral
TOPIRAMATE plasma
Homo sapiens
18.38 μg/mL
800 mg single, oral
TOPIRAMATE plasma
Homo sapiens
28.73 μg/mL
1200 mg single, oral
TOPIRAMATE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
59.8 μg × h/mL
100 mg single, oral
TOPIRAMATE plasma
Homo sapiens
57.3 μg × h/mL
100 mg single, oral
TOPIRAMATE plasma
Homo sapiens
311.2 μg × h/mL
400 mg single, oral
TOPIRAMATE plasma
Homo sapiens
350.3 mg × h/mL
400 mg single, oral
TOPIRAMATE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
18.7 h
100 mg single, oral
TOPIRAMATE plasma
Homo sapiens
23 h
400 mg single, oral
TOPIRAMATE plasma
Homo sapiens
23 h
200 mg single, oral
TOPIRAMATE plasma
Homo sapiens
22 h
800 mg single, oral
TOPIRAMATE plasma
Homo sapiens
20 h
1200 mg single, oral
TOPIRAMATE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
59%
unknown, unknown
TOPIRAMATE plasma
Homo sapiens

PubMed

Sample Use Guides

In Vivo Use Guide
Recommended dose: 400 mg orally per day in 2 divided doses of 200 mg each The dose should be achieved by titration: Week 1: 25 mg orally in the morning and 25 mg orally in the evening Week 2: 50 mg orally in the morning and 50 mg orally in the evening Week 3: 75 mg orally in the morning and 75 mg orally in the evening Week 4: 100 mg orally in the morning and 100 mg orally in the evening Week 5: 150 mg orally in the morning and 150 mg orally in the evening Week 6: 200 mg orally in the morning and 200 mg orally in the evening
Route of Administration: Oral
In Vitro Use Guide
0.3 to 10 uM topiramate 1 inhibited ATPA-evoked postsynaptic currents recorded from rat basolateral amygdala (BLA) interneurons
Substance Class Chemical
Record UNII
0H73WJJ391
Record Status Validated (UNII)
Record Version