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

Molecular Formula C8H8N2O3S
Molecular Weight 212.2271
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice.
2000 Sep 15
Concerns with antiepileptic drug initiation: safety, tolerability, and efficacy.
2001
Behavioural effects of the new anticonvulsants.
2001
Newer antiepileptic drugs: advantages and disadvantages.
2001 Aug
Clinical pharmacology and therapeutic use of the new antiepileptic drugs.
2001 Dec
Infantile spasms.
2001 Feb
Effect of immobilization stress on anticonvulsant actions and pharmacokinetics of zonisamide in mice.
2001 Jan
Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.
2001 Jan
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).
2001 Jan
New anticonvulsants for use in pediatric patients (part I).
2001 Mar-Apr
High-performance liquid chromatographic assay of zonisamide in human plasma using a non-porous silica column.
2001 May 5
Pharmacologic management of epilepsy in the elderly.
2001 May-Jun
Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling in rats.
2001 Nov
Refractory grand mal seizures with onset during infancy including severe myoclonic epilepsy in infancy.
2001 Nov
Zonisamide in West syndrome.
2001 Nov
Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation.
2001 Nov
Determination of effects of antiepileptic drugs on SNAREs-mediated hippocampal monoamine release using in vivo microdialysis.
2001 Oct
New and emerging prophylactic agents for migraine.
2002
Zonisamide add-on for drug-resistant partial epilepsy.
2002
The 'number needed to treat' with levetiracetam (LEV): comparison with the other new antiepileptic drugs (AEDs).
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
Smoldering myeloma associated with zonisamide treatment.
2002 Feb
Clinical pharmacology: drugs as a benefit and/or risk in sudden unexpected death in epilepsy?
2002 Feb
New antiepileptic drugs: review on drug interactions.
2002 Feb
Newer therapies in the drug treatment of epilepsy.
2002 Jan
[A case of infantile epileptic encephalopathy with frequent focal motor status convulsivus: successful treatment with zonisamide].
2002 Jan
Some common issues in the use of antiepileptic drugs.
2002 Mar
Long-term response to zonisamide in patients with West syndrome.
2002 May 28
Zonisamide treatment of bipolar disorder: a case report.
2002 Nov
[A case of bilateral perisylvian polymicrogyria with epileptic attacks of focal inhibitory seizure followed by complex partial seizure].
2002 Oct
Selective mutism and obsessive compulsive disorders associated with zonisamide.
2002 Oct
A casuistic rationale for the treatment of spastic and myocloni in a childhood neurodegenerative disease: neuronal ceroid lipofuscinosis of the type Jansky-Bielschowsky.
2002 Oct-Dec
[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
Use of anticonvulsants for treatment of neuropathic pain.
2002 Sep 10
Pharmacokinetics of mood stabilizers and new anticonvulsants.
2002 Winter
Selection criteria for the clinical use of the newer antiepileptic drugs.
2003
Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.
2003 Apr
Acute zonisamide overdose: a death revisited.
2003 Jun
Treating bipolar depression.
2003 Mar
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).
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:58:21 UTC 2021
Edited
by admin
on Fri Jun 25 20:58:21 UTC 2021
Record UNII
459384H98V
Record Status Validated (UNII)
Record Version
  • Download
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
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 N0000175753
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
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
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
WHO-VATC QN03AX15
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
LIVERTOX 1054
Created by admin on Fri Jun 25 20:58:21 UTC 2021 , Edited by admin on Fri Jun 25 20:58:21 UTC 2021
Code System Code Type Description
FDA UNII
459384H98V
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
IUPHAR
7047
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
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
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
MESH
C022189
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
RXCUI
39998
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 RxNorm
USP_CATALOG
1725003
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 USP-RS
EPA CompTox
68291-97-4
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
INN
5575
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
CAS
68291-97-4
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
LACTMED
Zonisamide
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
EVMPD
SUB00187MIG
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
MERCK INDEX
M11662
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 Merck Index
NCI_THESAURUS
C47790
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
DRUG BANK
DB00909
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
WIKIPEDIA
ZONISAMIDE
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
ChEMBL
CHEMBL750
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
HSDB
7293
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
DRUG CENTRAL
2872
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
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
TARGET -> INHIBITOR
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
URINE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

DOSE

FED CONDITION

Tmax PHARMACOKINETIC DOSE

ORAL ADMINISTRATION