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QuickView for topiramate (compound)

Summary
General Info

PubChem

PubChem Compound 10664802

PubChem Compound 10664802

Name:	topiramate
PubChem Compound ID:	10664802
Molecular formula:	C₁₂H₂₁NO₈S
Molecular weight:	339.363 g/mol

DrugBank

Identification

Name:	topiramate
Name (isomeric):	DB00273
Drug Type:	small molecule
Synonyms:	Topiramatum [INN-Latin]; Tipiramato [Spanish]; Topiramic acid; Tipiramate [French]; topiramate tablet; Topiramato [INN-Spanish]
Brand:	Topamax Sprinkle, Topamax
Category:	Anti-Obesity Agents, Neuroprotective Agents, Anticonvulsants
CAS number:	97240-79-4

Pharmacology

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.
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 inh... show more » 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. show less «
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... show more » 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 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. show less «
Absorption:	Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%.
Protein binding:	15-41% (over the blood concentration range of 0.5 - 250 mg/mL).
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.
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
Clearance:	Oral plasma cl=20 - 30 mL/min [in humans following oral administration]
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.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Phenytoin	Increased phenytoin/decreased topiramate
Acetazolamide	Additive renal carbonic anhydrase inhibition may occur increasing the risk of crystaluria and renal calculi. Increased risk of nephrolithiasis. Consider altnerate therapy.
Fosphenytoin	Increased phenytoin/decreased topiramate
Tobramycin	Increased risk of nephrotoxicity
Maraviroc	Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed.

Phenytoin	Increased phenytoin/decreased topiramate
Acetazolamide	Additive renal carbonic anhydrase inhibition may occur increasing the risk of crystaluria and renal calculi. Increased risk of nephrolithiasis. Consider altnerate therapy.
Fosphenytoin	Increased phenytoin/decreased topiramate
Tobramycin	Increased risk of nephrotoxicity
Maraviroc	Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed.
Triprolidine	The CNS depressants, Triprolidine and Topiramate, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Mestranol	Topiramate may decrease the effect of the oral contraceptive, Mestranol. An alternate form of contraception should be used during concomitant therapy.
Brinzolamide	As both brinzolamide and topiramate are carbonic anhydrase inhibitors, there is an increased risk of adverse effects.The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Avoid concurrent use of different carbonic anhydrase inhibitors when possible.
Ethinyl Estradiol	Topiramate may decrease the effect of the oral contraceptive, Ethinyl estradiol. An alternate form of contraception should be used during concomitant therapy.
Carbamazepine	Carbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.
Lithium	Topiramate could modify lithium levels
Chlorothiazide	Thiazide diuretics such as chlorothiazide may enhance the hypokalemic effect of topiramate. Thiazide diuretics may increase the serum concentration of topiramate. Monitor for increased topiramate concentrations/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary.

Targets

Gamma-aminobutyric-acid receptor subunit alpha-1

Sodium channel protein type 1 subunit alpha

Glutamate receptor, ionotropic kainate 1

Carbonic anhydrase 2

Carbonic anhydrase 4

Enzymes

Cytochrome P450 2C19

Cytochrome P450 3A4