General
Preferred name
TOPIRAMATE
Synonyms
RWJ 17021 ()
MCN 4853 ()
Topamax ()
MCN 4853, RWJ 17021 ()
Topomax ()
Topamac ()
Qudexy ()
Topina ()
RWJ-17021-000 ()
MCN-4853 ()
Epitoma ()
Topimax ()
Eprontia ()
Sincronil ()
Epitomax ()
Topamax Sprinkle ()
RWJ-17021 ()
USL-255 ()
(-)-topiramate ()
Topiramato ()
USL255 ()
Qudexy XR ()
Trokendi XR ()
Topiramate-d12 ()
P&D ID
PD000722
CAS
122-09-8
97240-79-4
1279037-95-4
Tags
available
drug
Approved by
PMDA
FDA
First approval
1996
Drug indication
Epilepsy
Anticonvulsant
Seizure disorder
Alcohol dependence
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The elimination half-life is reported to be in the range of 19-23 hours.[A175243] If coadministered with enzyme-inducers, the half-life can be changed to 12-15 hours.[A175246]
ROE
Topiramate is mainly eliminated unchanged.[A175243] It presents a dual elimination with the renal clearance being predominant and in absence of metabolic enzyme induction, over 80% of the eliminated dose is found unchanged in the urine.[A175246]
TOXICITY
Intraperitoneal topiramate LD50 in the rat is reported to be higher than 1500 mg/kg. The overdose of topiramate is presented by convulsions, drowsiness, speech disturbances, blurred vision, diplopia, mentation impaired, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness, depression, and metabolic acidosis. If overdose is reported rapidly, stomach lavage and induction of emesis is recommended accompanied by supportive treatment and hemodialysis.[A175258] In carcinogenic studies, topiramate was observed to produce tumors of smooth muscle origin in the urinary bladder in mice. Topiramate has also been shown to produce developmental toxicity shown by malformations and increased toxicity.[FDA label]
METABOLISM
Topiramate is known to be not extensively metabolized by CYP3A4[A175234] and the obtained metabolites are not known to be active.[A175237] The metabolism of topiramate only acts over about 20% of the administered dose. The restricted metabolism is characterized by reactions of glucuronidation, hydroxylation and hydrolysis which in order produces six minor metabolites representing individually less than 5% of the administered dose.[A175246]
ABSORPTION
Topiramate has good oral bioavailability of 81-95% and it presents a linear kinetic profile.[A175237] It reaches a maximal concentration of 1.73-28.7 mcg/ml after 2-4 hours of initial administration.[A175243, A175246] The plasma steady-state after multiple dosing is achieved after 4 days.[A175246] The concomitant administration of food produces changes in the absorption rate but not in the absorption extent.[A175246]
INDICATION
Topiramate is indicated for the following conditions:; ; - Monotherapy for partial onset or primary generalized tonic-clonic seizures in patients over 2 years of age. ; ; - Adjunctive therapy for partial onset seizures or primary generalized tonic-clonic seizures for adult and pediatric patients.; ; - Adjunctive therapy for seizures associated with Lennox-Gastaut syndrome in patients over 2 years of age.; ; - Prophylaxis of migraine headache in adults.[FDA label]; ; A seizure is an abnormal, unregulated electrical discharge occurring in the brain's cortical gray matter. This electrical response produces a transient interruption in the normal brain function which in order produces altered awareness, abnormal sensations, focal involuntary movements or convulsions. The type of seizure can be classified according to the type of onset followed by a type of seizure.[L5548]; ; A migraine headache is a [ulsating or throbbing pain that can be presented in one of both sides of the head and it can be worsened by external stimuli such as physical activity, light, sounds, and odors.[L5551]; ; Topiramate has been commonly investigated and used off-label for weight reduction in patients with obesity or diabetes.[A175240]
PHARMACODYNAMICS
In pre-clinical trials, topiramate was shown to be more potent than valproate but to be ineffective to block chemically-induced seizures even though it did increase the seizure threshold. In animal models of epilepsy, topiramate inhibited clonic motor seizures, absence-like seizures, sound-induced clonic and tonic seizures, tonic, clonic and wild running seizures in postischemia, and amygdala-kindled seizures.[A175249]; ; In trials performed with topiramate as an adjunct therapy in patients with partial seizures or Lennox-Gastaut syndrome, it was shown to produce a significant reduction in secondarily generalized, complex partial, and simple partial seizure rates. About 19% of the studied individuals presented a 75% reduction in seizures and about 4-7% became seizure free.[A175243]; ; When topiramate was studied clinically as a monotherapy, 33% of the studied individuals remain with topiramate use and 62% of these patients were found seizure-free for at least 3 months. In patients with generalized tonic-clonic seizures, over 50% of the topiramate-treated patients reported a seizure reduction and 13% reported seizure freedom.[A175252]; ; Topiramate has been studied on clinical trials related to alcohol dependence in which it has shown to produce moderate benefits on heavy drinking and on the number of drinks per day.[A175234]
MOA
Topiramate is known for having several mechanisms of action including voltage-dependent sodium channels, GABA receptors, and glutamate receptors.[A175243]; ; Topiramate facilitates GABA-A receptor activity at non-benzodiazepine receptor sites and reduces glutamate activity in AMPA and kainate receptors. It is also proposed to reduce mesolimbic dopaminergic activity.[A175234] As well, topiramate blocks the voltage-dependent sodium channels suppressing the spread of seizures.[A175243]; ; Topiramate is known to be an inhibitor of carbonic anhydrase, however, this mechanism has been questioned to be its main mechanism of action. From its inhibitory activity towards carbonic anhydrase, topiramate is known to selectively inhibit the subtype II and IV. It is not ruled out the potential inhibition on other subtypes.[A175249]
TOXICITY
Intraperitoneal topiramate LD50 in the rat is reported to be higher than 1500 mg/kg. The overdose of topiramate is presented by convulsions, drowsiness, speech disturbances, blurred vision, diplopia, mentation impaired, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness, depression, and metabolic acidosis. If overdose is reported rapidly, stomach lavage and induction of emesis is recommended accompanied by supportive treatment and hemodialysis.[A175258]; ; In carcinogenic studies, topiramate was observed to produce tumors of smooth muscle origin in the urinary bladder in mice. Topiramate has also been shown to produce developmental toxicity shown by malformations and increased toxicity.[FDA label]
ABSORPTION
Topiramate has good oral bioavailability of 81-95% and it presents a linear kinetic profile.[A175237] It reaches a maximal concentration of 1.73-28.7 mcg/ml after 2-4 hours of initial administration.[A175243, A175246] The plasma steady-state after multiple dosing is achieved after 4 days.[A175246]; ; The concomitant administration of food produces changes in the absorption rate but not in the absorption extent.[A175246]
DESCRIPTION
A multifunctional compound: inhibits carbonic anhydrases II and IV, positively modulates GABA-A receptor anion channels, blocks sodium channel alpha subunits and behaves as an antagonist at the ionotropic glutamate receptors (AMPA and kainate).
(GtoPdb)
PHARMACODYNAMICS
In pre-clinical trials, topiramate was shown to be more potent than valproate but to be ineffective to block chemically-induced seizures even though it did increase the seizure threshold. In animal models of epilepsy, topiramate inhibited clonic motor seizures, absence-like seizures, sound-induced clonic and tonic seizures, tonic, clonic and wild running seizures in postischemia, and amygdala-kindled seizures.[A175249] In trials performed with topiramate as an adjunct therapy in patients with partial seizures or Lennox-Gastaut syndrome, it was shown to produce a significant reduction in secondarily generalized, complex partial, and simple partial seizure rates. About 19% of the studied individuals presented a 75% reduction in seizures and about 4-7% became seizure free.[A175243] When topiramate was studied clinically as a monotherapy, 33% of the studied individuals remain with topiramate use and 62% of these patients were found seizure-free for at least 3 months. In patients with generalized tonic-clonic seizures, over 50% of the topiramate-treated patients reported a seizure reduction and 13% reported seizure freedom.[A175252] Topiramate has been studied on clinical trials related to alcohol dependence in which it has shown to produce moderate benefits on heavy drinking and on the number of drinks per day.[A175234]
MOA
Topiramate is known for having several mechanisms of action including voltage-dependent sodium channels, GABA receptors, and glutamate receptors.[A175243] Topiramate facilitates GABA-A receptor activity at non-benzodiazepine receptor sites and reduces glutamate activity in AMPA and kainate receptors. It is also proposed to reduce mesolimbic dopaminergic activity.[A175234] As well, topiramate blocks the voltage-dependent sodium channels suppressing the spread of seizures.[A175243] Topiramate is known to be an inhibitor of carbonic anhydrase, however, this mechanism has been questioned to be its main mechanism of action. From its inhibitory activity towards carbonic anhydrase, topiramate is known to selectively inhibit the subtype II and IV. It is not ruled out the potential inhibition on other subtypes.[A175249]
INDICATION
Topiramate is indicated for the following conditions: - Monotherapy for partial onset or primary generalized tonic-clonic seizures in patients over 2 years of age. - Adjunctive therapy for partial onset seizures or primary generalized tonic-clonic seizures for adult and pediatric patients. - Adjunctive therapy for seizures associated with Lennox-Gastaut syndrome in patients over 2 years of age. - Prophylaxis of migraine headache in adults.[FDA label] A seizure is an abnormal, unregulated electrical discharge occurring in the brain's cortical gray matter. This electrical response produces a transient interruption in the normal brain function which in order produces altered awareness, abnormal sensations, focal involuntary movements or convulsions. The type of seizure can be classified according to the type of onset followed by a type of seizure.[L5548] A migraine headache is a [ulsating or throbbing pain that can be presented in one of both sides of the head and it can be worsened by external stimuli such as physical activity, light, sounds, and odors.[L5551] Topiramate has been commonly investigated and used off-label for weight reduction in patients with obesity or diabetes.[A175240]
DESCRIPTION
GluK1-selective kainate antagonist
(Tocris Bioactive Compound Library)
DESCRIPTION
GluR5 antagonist; inhibits carbonic anhydrase (CA) II and IV
(Tocriscreen Plus)
DESCRIPTION
GluR5 antagonist; anticonvulsant
(Tocriscreen Total)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
3
Compound Sets
31
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
VGSC-DB
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
61
Molecular Weight
339.1
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
1
Rotatable Bonds
3
Ring Count
3
Aromatic Ring Count
0
cLogP
-0.4
TPSA
115.54
Fraction CSP3
1.0
Chiral centers
4.0
Largest ring
6.0
QED
0.74
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Carbonic anhydrase II
GABA-A receptor
anion channel
Sodium channel alpha subunit
Glutamate receptor ionotropic kainate
Carbonic anhydrase IV
Glutamate receptor ionotropic AMPA
Carbonic Anhydrase
GABAR
mGluR5
CA1, CA12, CA2, CA4, CA7, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GRIA1, GRIA2, GRIA3, GRIA4, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN7A, SCN8A, SCN9A
Calcium Channel
GABA Receptor
iGluR
Potassium Channel
Sodium Channel
Target Type
Ion Channels
MOA
voltage-gated sodium channel blocker
ionotropic glutamate receptor antagonist
Antagonist
Carbonic Anhydrase Type II Inhibitors
Kainate Receptor Antagonists
AMPA Receptor Antagonists
"Carbonic Anhydrase Type II Inhibitors
AMPA Receptor Antagonists"
carbonic anhydrase inhibitor, glutamate receptor antagonist, kainate receptor antagonist
Pathway
Membrane Transporter/Ion Channel
Metabolism
Neuroscience
Metabolic Enzyme/Protease
Neuronal Signaling
Primary Target
Kainate Receptors
Member status
member
Indication
epilepsy, migraine headache
Biosynthetic Origin
Carbohydrate
Therapeutic Indication
Antiepileptic
Therapeutic Class
CNS & PNS
Anticonvulsants
VGSC Target
Nav1.2
Source data
