Drug/Small Molecule:
topiramate

Overview
Properties
Genetics
Related Genes
Related Drugs
Related Diseases
Datasets
Downloads/LinkOuts

Overview

Generic Names:	Tipiramate [French]; Tipiramato [Spanish]; Topiramato [INN-Spanish]; Topiramatum [INN-Latin]; Topiramic acid; topiramate tablet
IUPAC Name:	2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
Trade Names:	Topamax; Topamax Sprinkle
PharmGKB Accession Id:	PA451728

Description

Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics, 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. [Wikipedia]

Indication

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.

ATC Therapeutic Category

N03AX:Other antiepileptics

Pharmacology and Interactions

Mechanism Of Action

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 GABA_A 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 glutamat 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.

Pharmacology

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.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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.

Protein Binding

15-41% (over the blood concentration range of 0.5 - 250 mg/mL).

Absorption

Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%.

Half Life

19 to 23 hours

Toxicity

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.

Chemical Properties

Chemical Formula:

C₁₂H₂₁NO₈S

SMILES Code:

CC1(O[C@@H]2CO[C@@]3([C@H]([C@@H]2O1)OC(O3)(C)C)COS(=O)(=O)N)C

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

339.362 / 339.0988

Curated Annotations ()

rs2304016 at chr2:165876749 in SCN2A, SCN2A2
The A allele of this SNP was associated with resistance to sodium channel-blocking anti-epileptic drugs in a Chinese patient population.

Variant Name:

SCN2A:IVS7-32A>G

Related Drugs:

carbamazepine, lamotrigine, oxcarbazepine, phenytoin, topiramate

Related Diseases:

Epilepsy

Evidence:

PMID:18784617
rs2032582 at chr7:86998554 in ABCB1
This variant maybe associated with drug resistance in chinese epilepsy patients. Sample size: 464 chinese epilepsy patients (270 drug responsive, 194 drug resistant).

Variant Name:

ABCB1: 2677T/A>G

Related Drugs:

carbamazepine, clobazam, clonazepam, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, topiramate, valproic acid, vigabatrin

Related Diseases:

Epilepsy

Evidence:

PMID:19450124
rs3789243 at chr7:87058822 in ABCB1
This variant maybe associated with drug resistance in chinese epilepsy patients. Sample size: 464 chinese epilepsy patients (270 drug responsive, 194 drug resistant).

Related Drugs:

carbamazepine, clobazam, clonazepam, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, topiramate, valproic acid, vigabatrin

Related Diseases:

Epilepsy

Evidence:

PMID:19450124