U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C8H8N2O3S
Molecular Weight 212.2271
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZONISAMIDE

SMILES

c1ccc2c(c1)c(CS(=O)(=O)N)no2

InChI

InChIKey=UBQNRHZMVUUOMG-UHFFFAOYSA-N
InChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including

Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and calcium channels, which leads to the suppression of neuronal hypersynchronization (i.e. convulsions). Sonisamide has also been found to potentiate dopaminergic and serotonergic neurotransmission but does not appear to potentiate syanptic activity by GABA (gamma amino butyric acid). Zonisamide binds to sodium channels and voltage sensitive calcium channels, which suppresses neuronal depolarization and hypersynchronization. Zonisamide also inhibits carbonic anhydrase to a weaker extent, but such an effect is not thought to contribute substantially to the drug's anticonvulsant activity. Zonisamide is approved in the United States, United Kingdom, and Australia for adjunctive treatment of partial seizures in adults and in Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZONEGRAN

Approved Use

ZONEGRAN is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.

Launch Date

9.5402879E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
18.4 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZONISAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
197.4 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZONISAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
63 h
unknown, oral
ZONISAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
60%
unknown, oral
ZONISAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
7.5 g single, oral
Overdose
Dose: 7.5 g
Route: oral
Route: single
Dose: 7.5 g
Sources:
unhealthy, 15 years
n = 1
Health Status: unhealthy
Age Group: 15 years
Sex: F
Population Size: 1
Sources:
Other AEs: Coma...
Other AEs:
Coma (1%)
Sources:
8.7 g single, oral
Overdose
Dose: 8.7 g
Route: oral
Route: single
Dose: 8.7 g
Sources:
unhealthy, 20 years
n = 1
Health Status: unhealthy
Age Group: 20 years
Sex: F
Population Size: 1
Sources:
Other AEs: Emesis...
Other AEs:
Emesis (1%)
Sources:
12.6 g single, oral
Overdose
Dose: 12.6 g
Route: oral
Route: single
Dose: 12.6 g
Sources:
unhealthy, 25 years
n = 1
Health Status: unhealthy
Age Group: 25 years
Sex: F
Population Size: 1
Sources:
Other AEs: Vomiting, Somnolence...
Other AEs:
Vomiting (1%)
Somnolence (1%)
Sources:
300 mg 2 times / day steady, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: steady
Dose: 300 mg, 2 times / day
Sources:
unhealthy, 35 years (range: 17.9-64.1 years)
n = 51
Health Status: unhealthy
Condition: refractory partial epilepsy
Age Group: 35 years (range: 17.9-64.1 years)
Sex: M+F
Population Size: 51
Sources:
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Disc. AE: Somnolence, Fatigue...
AEs leading to
discontinuation/dose reduction:
Somnolence (6%)
Fatigue (6%)
Ataxia (6%)
Anorexia (3%)
Attention concentration difficulty (2%)
Memory impairment (2%)
Mental retardation (2%)
Nausea (2%)
Vomiting (2%)
Weight loss (1%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Coma 1%
7.5 g single, oral
Overdose
Dose: 7.5 g
Route: oral
Route: single
Dose: 7.5 g
Sources:
unhealthy, 15 years
n = 1
Health Status: unhealthy
Age Group: 15 years
Sex: F
Population Size: 1
Sources:
Emesis 1%
8.7 g single, oral
Overdose
Dose: 8.7 g
Route: oral
Route: single
Dose: 8.7 g
Sources:
unhealthy, 20 years
n = 1
Health Status: unhealthy
Age Group: 20 years
Sex: F
Population Size: 1
Sources:
Somnolence 1%
12.6 g single, oral
Overdose
Dose: 12.6 g
Route: oral
Route: single
Dose: 12.6 g
Sources:
unhealthy, 25 years
n = 1
Health Status: unhealthy
Age Group: 25 years
Sex: F
Population Size: 1
Sources:
Vomiting 1%
12.6 g single, oral
Overdose
Dose: 12.6 g
Route: oral
Route: single
Dose: 12.6 g
Sources:
unhealthy, 25 years
n = 1
Health Status: unhealthy
Age Group: 25 years
Sex: F
Population Size: 1
Sources:
Weight loss 1%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Attention concentration difficulty 2%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Memory impairment 2%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Mental retardation 2%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Nausea 2%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Vomiting 2%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Anorexia 3%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Ataxia 6%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Fatigue 6%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Somnolence 6%
Disc. AE
100 mg 1 times / day multiple, oral (starting)
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, adult
n = 1336
Health Status: unhealthy
Condition: epilepsy
Age Group: adult
Population Size: 1336
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no
no
no
weak [IC50 267 uM]
weak [Ki 1076 uM]
weak
weak
weak
weak
weak
weak
weak
weak
yes (co-administration study)
Comment: <25% inhibition at levels approximately two-fold or greater than clinically relevant unbound serum concentrations. ; Coadministration of multiple dosing of zonisamide did not significantly affect the pharmacokinetic parameters of desipramine (CYP2D6 substrate).
Page: (Label) 3
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major [Km 312 uM]
yes (co-administration study)
Comment: The half-life of zonisamide following a 400 mg dose in patients concurrently on enzyme-inducing AEDs such as phenytoin, carbamazepine, or phenobarbital was between 27-38 hours (46 hr on the non-enzyme inducing AED, valproate).
Page: (Label) 2, (PMDA_I100) 20
minor [Km 179 uM]
minor [Km 188 uM]
yes
yes
yes
PubMed

PubMed

TitleDatePubMed
A solvent used for antiepileptic drugs increases serum and brain zonisamide concentrations in seizure-susceptible el mice.
2001 Aug
[Clinical features and treatment of refractory epilepsy in children].
2001 Dec
Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling in rats.
2001 Nov
Protein-losing cytomegalovirus gastritis in a patient with Stevens-Johnson syndrome.
2002
New and emerging prophylactic agents for migraine.
2002
Treatment of epilepsy in women of reproductive age: pharmacokinetic considerations.
2002
Zonisamide add-on for drug-resistant partial epilepsy.
2002
Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations.
2002 Apr
Combining lithium and anticonvulsants in bipolar disorder: a review.
2002 Dec
Antiepileptic drug therapy for adults: when to initiate and how to choose.
2002 Dec
Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs.
2002 Dec 20
Zonisamide in pediatric epilepsy: review of the Japanese experience.
2002 Feb
Using the new antiepilepsy drugs in children.
2002 Jan
Three new drugs for epilepsy: levetiracetam, oxcarbazepine, and zonisamide.
2002 Jan
Randomized controlled trial of zonisamide for the treatment of partial-onset seizures.
2002 Jun 11
New antiepileptic drugs.
2002 Mar
Some common issues in the use of antiepileptic drugs.
2002 Mar
Oral high-dose phenobarbital therapy for early infantile epileptic encephalopathy.
2002 Mar
Interaction between carbamazepine, zonisamide and voltage-sensitive Ca2+ channel on acetylcholine release in rat frontal cortex.
2002 Mar
Medical treatment of patients with infantile spasms.
2002 Mar-Apr
Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes.
2002 May
New antiepileptic drug therapies.
2002 Nov
Zonisamide treatment of bipolar disorder: a case report.
2002 Nov
New migraine preventive options: an update with pathophysiological considerations.
2002 Nov-Dec
[A case of bilateral perisylvian polymicrogyria with epileptic attacks of focal inhibitory seizure followed by complex partial seizure].
2002 Oct
Newer GABAergic agents for pharmacotherapy of infantile spasms.
2002 Oct
Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet.
2002 Oct
Selective mutism and obsessive compulsive disorders associated with zonisamide.
2002 Oct
[Monitoring serum levels of new antiepileptics].
2002 Sep
Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI).
2002 Sep
[Urolithiasis induced by combined ACTH and zonisamide treatment in a patient with startle induced epilepsy].
2002 Sep
Antiepileptic drug use during the first 12 months of vagus nerve stimulation therapy: a registry study.
2002 Sep 24
Pharmacokinetics of mood stabilizers and new anticonvulsants.
2002 Winter
Clinical care of pregnant women with epilepsy: neural tube defects and folic acid supplementation.
2003
Selection criteria for the clinical use of the newer antiepileptic drugs.
2003
Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect.
2003 Apr
Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.
2003 Apr
Zonisamide for weight loss in obese adults: a randomized controlled trial.
2003 Apr 9
Effects of concomitant antiepileptic drugs on serum carbamazepine concentration in epileptic patients: quantitative analysis based on extracellular water volume as a transforming factor.
2003 Jan
Visual hallucinations associated with zonisamide.
2003 Jan
Zonisamide-induced restless legs syndrome.
2003 Jan 14
Acute zonisamide overdose: a death revisited.
2003 Jun
Therapeutic drug monitoring of the newer antiepileptic drugs.
2003 Jun
The effect of systemic zonisamide (Zonegran) on thermal hyperalgesia and mechanical allodynia in rats with an experimental mononeuropathy.
2003 Jun
Oligohydrosis and fever in pediatric patients treated with zonisamide.
2003 Mar
Effects of valproate, phenytoin, and zonisamide on clonic and tonic seizures induced by acute and repeated exposure of mice to flurothyl.
2003 Mar
Treating bipolar depression.
2003 Mar
Review of the newer antiepileptic drugs.
2003 Mar
Therapeutics in pediatric epilepsy, Part 1: The new antiepileptic drugs and the ketogenic diet.
2003 Mar
[A five-year-old girl with epilepsy showing forced normalization due to zonisamide].
2003 May
Patents

Sample Use Guides

ZONEGRAN (zonisamide) is recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. ZONEGRAN should be administered once or twice daily, using 25 mg or 100 mg capsules. ZONEGRAN is given orally and can be taken with or without food. Capsules should be swallowed whole.
Route of Administration: Oral
In vitro studies have demonstrated that zonisamide (10–30 ug/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses (cultured mouse spinal cord neurons) or neuronal or glial uptake of [3H]-GABA (rat hippocampal slices).
Name Type Language
ZONISAMIDE
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
ZONISAMIDE [MART.]
Common Name English
ZONISAMIDE [EMA EPAR]
Common Name English
AD-810
Code English
ZONISAMIDE [WHO-DD]
Common Name English
CI-912
Code English
N03AX15
Code English
1,2-BENZISOXAZOLE-3-METHANESULFONAMIDE
Systematic Name English
ZONISAMIDE [USAN]
Common Name English
ZONISAMIDE [USP MONOGRAPH]
Common Name English
ZONISAMIDE [ORANGE BOOK]
Common Name English
ZONEGRAN
Brand Name English
ZONISAMIDE [MI]
Common Name English
ZONISAMIDE [INN]
Common Name English
ZONISAMIDE [JAN]
Common Name English
ZONISAMIDE [HSDB]
Common Name English
PD-110843
Code English
ZONISAMIDE [USP-RS]
Common Name English
ZONISAMIDE [VANDF]
Common Name English
EXCEGRAN
Brand Name English
Classification Tree Code System Code
WHO-ATC N03AX15
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
NCI_THESAURUS C264
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NDF-RT N0000175753
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EMA ASSESSMENT REPORTS ZONEGRAN (AUTHORIZED: EPILEPSIES, PARTIAL)
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
NDF-RT N0000008486
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WHO-VATC QN03AX15
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LIVERTOX 1054
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Code System Code Type Description
FDA UNII
459384H98V
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PRIMARY
IUPHAR
7047
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PRIMARY
NDF-RT
N0000185503
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
PUBCHEM
5734
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PRIMARY
MESH
C022189
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PRIMARY
RXCUI
39998
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PRIMARY RxNorm
USP_CATALOG
1725003
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PRIMARY USP-RS
EPA CompTox
68291-97-4
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PRIMARY
INN
5575
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PRIMARY
CAS
68291-97-4
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PRIMARY
LACTMED
Zonisamide
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PRIMARY
EVMPD
SUB00187MIG
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PRIMARY
MERCK INDEX
M11662
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PRIMARY Merck Index
NCI_THESAURUS
C47790
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PRIMARY
DRUG BANK
DB00909
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PRIMARY
WIKIPEDIA
ZONISAMIDE
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PRIMARY
ChEMBL
CHEMBL750
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PRIMARY
HSDB
7293
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PRIMARY
DRUG CENTRAL
2872
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PRIMARY