Zonisamide

Summary

Zonisamide (CHEMBL750) is an approved small-molecule anticonvulsant (ATC N03AX15) targeting CA1, CA12, and CA7; indicated across 20 conditions including epilepsy and visual epilepsy.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N03AX15
• Targets: 3 (CA1, CA12, CA7)
• Indications: 20 conditions
• Clinical trials: 64
• Chemistry: 212.23 Da · C8H8N2O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL750
Name	Zonisamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5734
ChEBI	CHEBI:10127
ATC	N03AX15
Molecular formula	C8H8N2O3S
Molecular weight	212.23
InChIKey	UBQNRHZMVUUOMG-UHFFFAOYSA-N

SMILES: C1=CC=C2C(=C1)C(=NO2)CS(=O)(=O)N

IUPAC name: 1,2-benzoxazol-3-ylmethanesulfonamide

ChEBI definition: A 1,2-benzoxazole compound having a sulfamoylmethyl substituent at the 3-position.

Pharmacological roles (ChEBI): anticonvulsant, antioxidant, central nervous system drug, protective agent, T-type calcium channel blocker.

Also known as: AD-810, CI-912, Excegran, N03AX15, PD-110843, Zonegran, Zonisade, Zonisamida, Zonisamide, Zonisamide mylan, zonisamide, SID29215225

Parent form; salt/anhydrous children: CHEMBL1596271

Patent coverage: 4,091 distinct patent families (16,649 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 16,379 (98%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CA1	carbonic anhydrase 1	Inhibition	7.25	0%	P00915
CA12	carbonic anhydrase 12	Inhibition	4.96	0.2%	O43570
CA7	carbonic anhydrase 7	Inhibition	6.93	1.6%	P43166

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: Prelamin-A/C, Amine oxidase [flavin-containing], Carbonic anhydrase 3, Amine oxidase [flavin-containing] B, Carbonic anhydrase 2, Carbonic anhydrase, Carbonic anhydrase V, Carbonic anhydrase 7, Carbonic anhydrase 1, Amine oxidase [flavin-containing] B.

Bioactivity

ChEMBL activities: 162 potent at pChembl ≥ 5 of 175 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CA7	9.05	Ki	0.9	nM	CHEMBL_ACT_23227334
CA12	8.42	Ki	3.8	nM	CHEMBL_ACT_23227361
CA9	8.3	Ki	5	nM	CHEMBL_ACT_1760577
CA9	8.3	Ki	5	nM	CHEMBL_ACT_2939253
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_10950766
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_13440659
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_13910710
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_1428891
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_2496780
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_2949495
CA9	8.29	Ki	5.1	nM	CHEMBL_ACT_7957532
CA2	7.99	Ki	10.3	nM	CHEMBL_ACT_1520838
CA2	7.98	Ki	10.4	nM	CHEMBL_ACT_23227307
CA5A	7.7	Ki	20	nM	CHEMBL_ACT_2569788
CA5A	7.7	Ki	20	nM	CHEMBL_ACT_2921013
CA5A	7.7	Ki	20	nM	CHEMBL_ACT_2949491
CA5A	7.7	Ki	20	nM	CHEMBL_ACT_5236256
CA5A	7.69	Ki	20.6	nM	CHEMBL_ACT_1520840
CA5A	7.69	Kd	20.6	nM	CHEMBL_ACT_1944012
CA2	7.46	Ki	35	nM	CHEMBL_ACT_10946405
CA2	7.46	Ki	35	nM	CHEMBL_ACT_10950720
CA2	7.46	Ki	35	nM	CHEMBL_ACT_12655978
CA2	7.46	Ki	35	nM	CHEMBL_ACT_13286816
CA2	7.46	Ki	35	nM	CHEMBL_ACT_13407614
CA2	7.46	Ki	35	nM	CHEMBL_ACT_13440701
CA2	7.46	Ki	35	nM	CHEMBL_ACT_13866459
CA2	7.46	Ki	35	nM	CHEMBL_ACT_13910731
CA2	7.46	Ki	35	nM	CHEMBL_ACT_14661462
CA2	7.46	Ki	35	nM	CHEMBL_ACT_15108415
CA2	7.46	Ki	35	nM	CHEMBL_ACT_15143686

Target pathways

Aggregated over 3 target gene(s): CA1, CA12, CA7.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	3	CA1, CA12, CA7
Reversible hydration of carbon dioxide	3	CA1, CA12, CA7
Erythrocytes take up carbon dioxide and release oxygen	1	CA1
Erythrocytes take up oxygen and release carbon dioxide	1	CA1
Cytokine Signaling in Immune system	1	CA1
O2/CO2 exchange in erythrocytes	1	CA1
Immune System	1	CA1
Transport of small molecules	1	CA1
Interleukin-12 family signaling	1	CA1
Signaling by Interleukins	1	CA1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	CA1
Interleukin-12 signaling	1	CA1

Dominant GO biological processes

GO term	Targets
response to fructose	1
estrous cycle	1
chloride ion homeostasis	1
positive regulation of synaptic transmission, GABAergic	1
obsolete positive regulation of cellular pH reduction	1
regulation of intracellular pH	1
neuron cellular homeostasis	1
regulation of chloride transport	1

Indications & clinical

Indications

20 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
epilepsy	4	MONDO:0005027	EFO:0000474
visual epilepsy	4	MONDO:0001386	HP:0001250
focal epilepsy	4	MONDO:0005384	EFO:0004263
eating disorder	3	MONDO:0005451	EFO:0005203
schizoaffective disorder	3	MONDO:0005487	EFO:0005411
complex partial epilepsy	3	MONDO:0006710	EFO:1000877
alcohol abuse	3	MONDO:0002046	MONDO:0002046
migraine disorder	3	MONDO:0005277	MONDO:0005277
essential tremor	2	MONDO:0003233	EFO:0003108
obesity disorder	2	MONDO:0011122	EFO:0001073
hearing loss disorder	2	MONDO:0005365	EFO:0004238
Parkinson disease	2	MONDO:0005180	MONDO:0005180
nicotine dependence	1	MONDO:0008575	EFO:0003768
cocaine dependence	1	MONDO:0005186	EFO:0002610
noise induced hearing loss	1	MONDO:0013098	EFO:1001254

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 64.

Phase distribution

Phase	Trials
PHASE3	20
PHASE4	16
Not specified	11
PHASE2	9
PHASE1	4
PHASE1/PHASE2	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06534502	PHASE4	NOT_YET_RECRUITING	Study of the Pharmacokinetics, Safety, and Tolerability of ZONISADE in Children 1 Month to 17 Years of Age With Partial-onset Seizures
NCT06967012	PHASE4	RECRUITING	A Clinical Study on the Efficacy and Safety of Zonisamide as a First Add-On Treatment in Epileptic Seizures
NCT00047567	PHASE4	TERMINATED	Open-label Adjunctive Zonisamide for Bipolar Disorder
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00259636	PHASE4	WITHDRAWN	Zonisamide for Fibromyalgia & Migraine
NCT00595556	PHASE4	COMPLETED	Zonisamide vs. Placebo in the Treatment of Alcohol Dependence
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00855738	PHASE4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01630057	PHASE4	COMPLETED	Evaluation of the Efficacy and Safety of Adjunctive Zonisamide vs Replacement With Zonisamide of the Last Added Antiepileptic Drug
NCT03034538	PHASE4	SUSPENDED	An Open-Label Tolerability and Exploratory Efficacy Study of Zonisamide for Dyskinesias in Parkinson’s Disease
NCT00056576	PHASE3	COMPLETED	Dose Response Study of Zonegran in Patients With Newly Diagnosed Epilepsy
NCT00221442	PHASE3	COMPLETED	Zonegran in the Treatment of Binge Eating Disorder Associated With Obesity
NCT00292461	PHASE3	COMPLETED	A Study for Evaluating the Efficacy and Safety of Zonisamide and Lamotrigine (Lamictal) for Subjects With Refractory Simple Partial, Complex Partial or Partial With Secondary Generalized Seizures
NCT00327717	PHASE3	COMPLETED	Evaluating the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures
NCT00363376	PHASE3	COMPLETED	A Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain
NCT00401973	PHASE3	COMPLETED	Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine
NCT00477295	PHASE3	COMPLETED	A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy
NCT00566254	PHASE3	COMPLETED	Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study)
NCT00692003	PHASE3	TERMINATED	Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
NCT00693017	PHASE3	TERMINATED	Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy
NCT00848549	PHASE3	COMPLETED	Assessing The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures
NCT01136954	PHASE3	COMPLETED	A Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Extension Study)
NCT01766128	PHASE2/PHASE3	WITHDRAWN	Study of Zonisamide in Early Parkinson Disease
NCT01806805	PHASE3	COMPLETED	Efficacy Trial of Zonisamide for Myoclonus Dystonia
NCT02368431	PHASE3	TERMINATED	Effectiveness of Zonisamide in Alcohol Dependent Veterans
NCT02900352	PHASE3	COMPLETED	Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
NCT02901041	PHASE3	COMPLETED	Interdisciplinary Study of A Novel Anticonvulsant in Alcoholism
NCT04388319	PHASE3	COMPLETED	Zonisamide/Bupropion Effects on Switching to Electronic Cigarettes
NCT05205811	PHASE3	COMPLETED	The Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette
NCT06347497	PHASE3	COMPLETED	Zonisamide Versus Topiramate in Migraine
NCT06361446	PHASE3	UNKNOWN	Zonisamide Versus Propranolol in Migraine
NCT05134857	PHASE2	RECRUITING	The Zonisamide and Reinforcement for Reducing Alcohol Use (ZARRA) Study
NCT00055484	PHASE2	COMPLETED	A Study to Measure the Safety and Effectiveness of Zonisamide in Subjects With Migraine Headache
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 3 clinical and 7 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

82 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ACETAMINOPHEN	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
ACETAZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
BORTEZOMIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
BRINZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
CELECOXIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
CHLORTHALIDONE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
COUMARIN	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
DICHLORPHENAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
DOBUTAMINE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
DORZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
ETHOXZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
FAMOTIDINE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
FUROSEMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
IMATINIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
INDAPAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
LACOSAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
LEVETIRACETAM	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
MAFENIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
METHAZOLAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
NILOTINIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
SALICYLIC ACID	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
SULFANILAMIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
SULPIRIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
TOPIRAMATE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
TRICHLORMETHIAZIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
TRIENTINE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
VALDECOXIB	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
VERALIPRIDE	ChEMBL	Phase 4 (approved)	CA1, CA12, CA7
CAFFEIC ACID	ChEMBL	Phase 3	CA1, CA12, CA7
CURCUMIN	ChEMBL	Phase 3	CA1, CA12, CA7
P-TOLUENESULFONAMIDE	ChEMBL	Phase 3	CA1, CA12, CA7
QUERCETIN	ChEMBL	Phase 3	CA1, CA12, CA7
RESVERATROL	ChEMBL	Phase 3	CA1, CA12, CA7
SACCHARIN	ChEMBL	Phase 3	CA1, CA12, CA7
SPERMIDINE	ChEMBL	Phase 3	CA1, CA12, CA7
CARZENIDE	ChEMBL	Phase 2	CA1, CA12, CA7
COUMAPHOS	ChEMBL	Phase 2	CA1, CA12, CA7
ELLAGIC ACID	ChEMBL	Phase 2	CA1, CA12, CA7
GALLIC ACID	ChEMBL	Phase 2	CA1, CA12, CA7
INDISULAM	ChEMBL	Phase 2	CA1, CA12, CA7
IROSUSTAT	ChEMBL	Phase 2	CA1, CA12, CA7
PCI-27483	ChEMBL	Phase 2	CA1, CA12, CA7
SONEPIPRAZOLE	ChEMBL	Phase 2	CA1, CA12, CA7
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	CA1, CA12
HYDROQUINONE	ChEMBL	Phase 4 (approved)	CA1, CA12
PHENOL	ChEMBL	Phase 4 (approved)	CA1, CA12
PYRITHIONE ZINC	ChEMBL	Phase 4 (approved)	CA12, CA7
SULTHIAME	ChEMBL	Phase 4 (approved)	CA1, CA7
PRITELIVIR	ChEMBL	Phase 3	CA1, CA12
THIMEROSAL	ChEMBL	Phase 3	CA12, CA7
BENZYLSULFAMIDE	ChEMBL	Phase 2	CA1, CA12
DAIDZEIN	ChEMBL	Phase 2	CA12, CA7
DITIOCARB	ChEMBL	Phase 2	CA1, CA12
FLAVONE	ChEMBL	Phase 2	CA1, CA12
ISOQUERCETIN	ChEMBL	Phase 2	CA12, CA7
LUTEOLIN	ChEMBL	Phase 2	CA12, CA7
PUERARIN	ChEMBL	Phase 2	CA12, CA7
SODIUM CYCLAMATE	ChEMBL	Phase 2	CA12, CA7
SULFASUCCINAMIDE	ChEMBL	Phase 2	CA1, CA12
CHLOROTHIAZIDE	ChEMBL	Phase 4 (approved)	CA1