ETHOSUXIMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C7H11NO2
Molecular Weight	141.1677
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1(C)CC(=O)NC1=O

InChI

InChIKey=HAPOVYFOVVWLRS-UHFFFAOYSA-N

InChI=1S/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)

HIDE SMILES / InChI

Molecular Formula	C7H11NO2
Molecular Weight	141.1677
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.drugbank.ca/drugs/DB00593
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/ethosuximide.html

Ethosuximide is a succinimide anticonvulsant, used in the treatment of epilepsy. Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli. Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Ethosuximide is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated T-type calcium channel alpha-1G subunit 8 Target ID: CHEMBL4641 Sources: http://www.drugbank.ca/drugs/DB00593	Inhibitor 8504
Voltage-gated T-type calcium channel 19 Target ID: CHEMBL2362995 Sources: http://www.genome.jp/dbget-bin/www_bget?hsa:8911	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Absence epilepsy 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/40253_Ethosuximide_Prntlbl.pdf	Primary		Approved 8583	Ethosuximide Approved Use Ethosuximide is indicated for the control of absence (petit mal) epilepsy. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
21 μg/mL REVIEW https://www.medicines.org.uk/emc/product/9762/smpc	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		ETHOSUXIMIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
12.4 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8799524	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOSUXIMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
915 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8799524	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOSUXIMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
53.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8799524	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOSUXIMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
30.4 h REVIEW https://www.medicines.org.uk/emc/product/9762/smpc	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOSUXIMIDE plasma	Homo sapiens population: UNKNOWN age: CHILD sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
78.2% EXPERIMENT https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13802	unknown, unknown		ETHOSUXIMIDE serum	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 60 mg/kg, 1 times / day Route: oral Route: multiple Dose: 60 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	unhealthy, 4-13 Health Status: unhealthy Age Group: 4-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	Disc. AE: Nervous system disorder, Digestion impaired... AEs leading to discontinuation/dose reduction: Nervous system disorder (8.4%) Digestion impaired (5.8%) Rash (3.9%) Fatigue (1.9%) Headache (1.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/23167925
1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6818076	unhealthy, 4-14 Health Status: unhealthy Age Group: 4-14 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6818076	DLT: Drowsiness... Dose limiting toxicities: Drowsiness (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/6818076
1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf	Disc. AE: Blood dyscrasia, Lupus erythematosus systemic... AEs leading to discontinuation/dose reduction: Blood dyscrasia Lupus erythematosus systemic Suicidal behavior Suicidal ideation Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf

AEs

AE	Significance	Dose	Population
Fatigue	1.9% Disc. AE	60 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 60 mg/kg, 1 times / day Route: oral Route: multiple Dose: 60 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	unhealthy, 4-13 Health Status: unhealthy Age Group: 4-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23167925
Headache	1.9% Disc. AE	60 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 60 mg/kg, 1 times / day Route: oral Route: multiple Dose: 60 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	unhealthy, 4-13 Health Status: unhealthy Age Group: 4-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23167925
Rash	3.9% Disc. AE	60 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 60 mg/kg, 1 times / day Route: oral Route: multiple Dose: 60 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	unhealthy, 4-13 Health Status: unhealthy Age Group: 4-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23167925
Digestion impaired	5.8% Disc. AE	60 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 60 mg/kg, 1 times / day Route: oral Route: multiple Dose: 60 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	unhealthy, 4-13 Health Status: unhealthy Age Group: 4-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23167925
Nervous system disorder	8.4% Disc. AE	60 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 60 mg/kg, 1 times / day Route: oral Route: multiple Dose: 60 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23167925	unhealthy, 4-13 Health Status: unhealthy Age Group: 4-13 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23167925
Drowsiness	16.7% DLT	1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6818076	unhealthy, 4-14 Health Status: unhealthy Age Group: 4-14 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6818076
Blood dyscrasia	Disc. AE	1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf
Lupus erythematosus systemic	Disc. AE	1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf
Suicidal behavior	Disc. AE	1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf
Suicidal ideation	Disc. AE	1.5 g 1 times / day multiple, oral Recommended Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/012380s032lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 729 CYP2A6 626 CYP1A2 1197

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/; https://www.tandfonline.com/doi/abs/10.3109/00498259309059384	major	yes (co-administration study) Comment: Rifampin increased ethosuximide CL/F by 63 % Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/; https://www.tandfonline.com/doi/abs/10.3109/00498259309059384
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/	minor
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/	no
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12637244/	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4887	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4887
ChemicalBook	CB1420630	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1420630
eMolecules	28291654	https://www.emolecules.com/cgi-bin/more?vid=28291654
eMolecules	538136	https://www.emolecules.com/cgi-bin/more?vid=538136
MolPort	MolPort-003-666-417	https://www.molport.com/shop/molecule-link/MolPort-003-666-417

PubMed

Title	Date	PubMed
Isobolographic and subthreshold analysis of interactions among felbamate and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice.	2004-10	15461671
Simple and rapid micellar electrokinetic capillary chromatographic method for simultaneous determination of four antiepileptics in human serum.	2004-10	15386509
Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines.	2004-10	15380158
Antiepileptic drug treatment of nonconvulsive seizures induced by experimental focal brain ischemia.	2004-10	15140918
[Long-term follow-up of a case of eyelid myoclonia with absences].	2004-09	15461025
PXR and the regulation of apoA1 and HDL-cholesterol in rodents.	2004-09	15225665
[Anticonvulsant hypersensitivity syndrome].	2004-08-08	15384865
Effect of YM928, a novel AMPA receptor antagonist, on seizures in EL mice and kainate-induced seizures in rats.	2004-08	15322731
The activity of antiepileptic drugs as histone deacetylase inhibitors.	2004-07	15230695
Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models.	2004-07	15158698
[Modulating effect of anticonvulsive agents on Ca2+ dependent membrane fusion in cell-free model of neurosecretion].	2004-05-18	15143522
Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy.	2004-05	15082137
Is the persistent sodium current a specific target of anti-absence drugs?	2004-04-29	15076732
Pharmacology of recombinant low-voltage activated calcium channels.	2004-04	15078185
Treatment with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants.	2004-03	14978727
[Idiopathic epilepsies: some therapeutic aspects].	2004-01-31	14752722
Effects of the combination of valproate and ethosuximide on spike wave discharges in WAG/Rij rats.	2004-01-21	15246119
Speech and language deterioration in benign rolandic epilepsy.	2004-01	15032386
Effects of 2-[N-(4-chlorophenyl)-N-methylamino]-4H-pyrido[3.2-e]-1,3-thiazin-4-one (YM928), an orally active alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, in models of generalized epileptic seizure in mice and rats.	2004-01	14569061
Is spontaneous high-voltage rhythmic spike discharge in Long Evans rats an absence-like seizure activity?	2004-01	12826656
Hippocampal afterdischarges in rats. I. Effects of antiepileptics.	2004	15312006
Cortical-area specific block of genetically determined absence seizures by ethosuximide.	2004	14667436
Riluzole enhances the anti-seizure action of conventional antiepileptic drugs against pentetrazole-induced convulsions in mice.	2003-12-23	15156069
Assessment of anticonvulsant effectiveness and safety in patients with Angelman's syndrome using an Internet questionnaire.	2003-12-15	14735775
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003-11-17	14612892
Effects of antiepileptic drugs on refractory seizures in the intact immature corticohippocampal formation in vitro.	2003-11	14636342
Some antiepileptic compounds impair learning by rats in a Morris water maze.	2003-10-07	14527179
Ethosuximide induced agranulocytosis.	2003-10	13129598
Reversal of experimental neuropathic pain by T-type calcium channel blockers.	2003-09	14499432
Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats.	2003-09	12970103
Absence seizures in patients with localization-related epilepsy.	2003-09	12907277
Epilepsy.	2003-07	12838266
Effects of Cyperus articulatus compared to effects of anticonvulsant compounds on the cortical wedge.	2003-07	12787951
Influence of SIB 1893, a selective mGluR5 receptor antagonist, on the anticonvulsant activity of conventional antiepileptic drugs in two models of experimental epilepsy.	2003-06-03	14704469
Thermal and rheological study of lipophilic ethosuximide suppositories.	2003-06	12791414
Targeting thalamic nuclei is not sufficient for the full anti-absence action of ethosuximide in a rat model of absence epilepsy.	2003-05	12837561
Effect of topiramate on the anticonvulsant activity of conventional antiepileptic drugs in two models of experimental epilepsy.	2003-05	12752462
Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes.	2003-03	12637244
Influence of vigabatrin, a novel antiepileptic drug, on the anticonvulsant activity of conventional antiepileptics in pentetrazole-induced seizures in mice.	2003-02-10	14506315
Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation.	2003-01-02	12531459
Effects of concomitant antiepileptic drugs on serum carbamazepine concentration in epileptic patients: quantitative analysis based on extracellular water volume as a transforming factor.	2003-01	12607943
Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms.	2003	14510623
Clinical trials for treatment of primary generalized epilepsies.	2003	12919339
Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents.	2003	12917940
Absence seizures in children.	2002-12	12603880
[Epilepsy with continuous spikes and waves during slow sleep].	2002	12483863
Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons.	1992-12	1336826
In vivo evidence that ethosuximide is a substrate for cytochrome P450IIIA.	1992	1438522
Effect of ethosuximide on rest tremor in the MPTP monkey model.	1992	1350061
Ethosuximide and tremor in Parkinson's disease: a pilot study.	1992	1350060

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Seizures Initial dose: 500 mg (10 mL) orally daily Maintenance dose: Dosage may be increased by small increments, for example 250 mg daily every 4 to 7 days, until optimal seizure control with minimal side effects is achieved.

Route of Administration: Oral

In Vitro Use Guide

3 mM ethosuximide blocked 20 and 35% of the I(Ba) at a HP of -100 and -60 mV

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:42:30 GMT 2025` Edited by `admin` on `Mon Mar 31 18:42:30 GMT 2025`
Record UNII	5SEH9X1D1D
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ZARONTIN

Preferred Name

English

ETHOSUXIMIDE

Official Name

English

ETHOSUXIMIDE [USP MONOGRAPH]

Common Name

English

ETHOSUXIMIDE [USP-RS]

Common Name

English

ETHOSUXIMIDE [ORANGE BOOK]

Common Name

English

ETHOSUXIMIDE [JAN]

Common Name

English

ethosuximide [INN]

Common Name

English

PM-671

Code

English

ETHOSUXIMIDE [EP MONOGRAPH]

Common Name

English

PYKNOLEPSINUM

Common Name

English

NSC-64013

Code

English

CN-10,395

Code

English

ETHOSUXIMIDE [USAN]

Common Name

English

CI-366

Code

English

ETHOSUXIMIDE [MART.]

Common Name

English

ETHOSUXIMIDUM [WHO-IP LATIN]

Common Name

English

ETHOSUXIMIDE [WHO-IP]

Common Name

English

ETHOSUXIMIDE [VANDF]

Common Name

English

2,5-PYRROLIDINEDIONE, 3-ETHYL-3-METHYL-, (±)-

Systematic Name

English

Ethosuximide [WHO-DD]

Common Name

English

ETHOSUXIMIDE [HSDB]

Common Name

English

ETHOSUXIMIDE [MI]

Common Name

English

(±)-2-ETHYL-2-METHYLSUCCINIMIDE

Systematic Name

English

CN-10395

Code

English

Classification Tree Code System Code

NDF-RT

N0000008486