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.

Mechanism of action

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.

Target	Actions	Organism
AVoltage-dependent T-type calcium channel subunit alpha-1G	inhibitor	Humans

Absorption

Bioavailability following oral administration is 93%.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic, via CYP3A4 and CYP2E1.

Route of elimination

Not Available

Half-life

53 hours

Clearance

Not Available

Adverse Effects

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Toxicity

Acute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of CNS depression can be increased when Ethosuximide is combined with 1,2-Benzodiazepine.
Abametapir	The serum concentration of Ethosuximide can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Ethosuximide can be increased when combined with Abatacept.
Acarbose	The risk or severity of hypoglycemia can be increased when Ethosuximide is combined with Acarbose.
Acebutolol	Ethosuximide may increase the arrhythmogenic activities of Acebutolol.
Aceclofenac	The risk or severity of hyperkalemia can be increased when Ethosuximide is combined with Aceclofenac.
Acemetacin	The risk or severity of hyperkalemia can be increased when Ethosuximide is combined with Acemetacin.
Acetaminophen	Ethosuximide may increase the hepatotoxic activities of Acetaminophen.
Acetazolamide	The risk or severity of CNS depression can be increased when Ethosuximide is combined with Acetazolamide.
Acetohexamide	The risk or severity of hypoglycemia can be increased when Ethosuximide is combined with Acetohexamide.

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Food Interactions

Avoid alcohol.
Take with food.

Products

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Product Images

International/Other Brands

Emeside (Chemidex) / Ethymal (Apotex Europe) / Etoxin (Apsen) / Petimid (Osel) / Petinimid (Gerot) / Petnidan (Desitin) / Suxilep (Jenapharm) / Suxinutin (McNeil) / Zarondan (Pfizer)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Zarontin	Capsule	250 mg/1	Oral	Parke-Davis Div of Pfizer Inc	2000-09-22	Not applicable
Zarontin	Capsule	250 mg	Oral	Searchlight Pharma Inc	1960-12-31	Not applicable
Zarontin Syrup	Syrup	250 mg / 5 mL	Oral	Searchlight Pharma Inc	1964-12-31	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Ethosuximide	Capsule, liquid filled	250 mg/1	Oral	Bionpharma Inc.	2016-10-21	Not applicable
Ethosuximide	Capsule	250 mg/1	Oral	Chartwell Rx, Llc	2015-09-09	Not applicable
Ethosuximide	Capsule	250 mg/1	Oral	Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.	2015-09-09	Not applicable
Ethosuximide	Capsule	250 mg/1	Oral	Strides Pharma Science Limited	2019-05-15	Not applicable
Ethosuximide	Capsule	250 mg/1	Oral	Avera McKennan Hospital	2015-10-30	2017-05-24
Ethosuximide	Capsule	250 1/1	Oral	Zydus Pharmaceuticals Usa, Inc.	2012-10-10	Not applicable
Ethosuximide	Capsule	250 mg/1	Oral	Akorn	2008-09-01	Not applicable
Ethosuximide	Solution	250 mg/5mL	Oral	Greenstone LLC	2020-02-21	Not applicable
Ethosuximide	Capsule	250 mg/1	Oral	Teva	2002-11-01	2017-04-30
Ethosuximide	Solution	250 mg/5mL	Oral	Teva Pharmaceuticals USA, Inc.	1994-07-01	2019-10-31

Chemical Identifiers

UNII: 5SEH9X1D1D
CAS number: 77-67-8
InChI Key: HAPOVYFOVVWLRS-UHFFFAOYSA-N
InChI: InChI=1S/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)
IUPAC Name: 3-ethyl-3-methylpyrrolidine-2,5-dione
SMILES: CCC1(C)CC(=O)NC1=O

References

Synthesis Reference

Miller, C.A. and Long, L.M.; U.S. Patent 2,993,835; July 25,1961; assigned to Parke, Davis and Company.

General References

Patsalos PN: Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies. Epilepsia. 2005;46 Suppl 9:140-8. [Article]
Coulter DA, Huguenard JR, Prince DA: Specific petit mal anticonvulsants reduce calcium currents in thalamic neurons. Neurosci Lett. 1989 Mar 13;98(1):74-8. [Article]
Coulter DA, Huguenard JR, Prince DA: Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol. 1989 Jun;25(6):582-93. [Article]
Coulter DA, Huguenard JR, Prince DA: Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: calcium current reduction. Br J Pharmacol. 1990 Aug;100(4):800-6. [Article]
Kostyuk PG, Molokanova EA, Pronchuk NF, Savchenko AN, Verkhratsky AN: Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons. Neuroscience. 1992 Dec;51(4):755-8. [Article]

External Links

Human Metabolome Database: HMDB0014731
KEGG Drug: D00539
KEGG Compound: C07505
PubChem Compound: 3291
PubChem Substance: 46507617
ChemSpider: 3175
BindingDB: 50240424
RxNav: 4135
ChEBI: 4887
ChEMBL: CHEMBL696
Therapeutic Targets Database: DAP000526
PharmGKB: PA449533
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Ethosuximide

FDA label

Download (174 KB)

MSDS

Download (73.5 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Unknown Status	Treatment	Epilepsies	1
3	Completed	Treatment	Childhood Absence Epilepsy / Epilepsies / Petit Mal Epilepsy / Seizures	1
3	Recruiting	Treatment	Irritable Bowel Syndrome (IBS)	1
3	Recruiting	Treatment	Ketogenic Dieting / Petit Mal Epilepsy	1
2	Active Not Recruiting	Treatment	Irritable Bowel Syndrome (IBS)	1
2	Completed	Supportive Care	Cancer / Peripheral neuropathy	1
2	Completed	Treatment	Neuropathic Pain Diagnostic Questionnaire (DN4) ≥ 4 / Neuropathic Traumatic Pain / Pain NRS ≥ 4 / Peripheral Neuropathic Pain	1
2	Recruiting	Treatment	Peripheral Neuropathic Pain	1
2	Terminated	Treatment	Complex Regional Pain Syndrome (RSD)	1
1, 2	Terminated	Prevention	Migraine	1

Pharmacoeconomics

Manufacturers

Banner pharmacaps inc
Convenant pharma inc
Parke davis div warner lambert co
Mikart inc
Pharmaceutical assoc inc div beach products
Teva pharmaceuticals usa
Parke davis pharmaceutical research div warner lambert co

Packagers

Barr Pharmaceuticals
Catalent Pharma Solutions
Mikart Inc.
Pfizer Inc.
Pharmaceutical Association
Pliva Inc.
Swiss Caps Ag
Teva Pharmaceutical Industries Ltd.
Versapharm Inc.

Dosage Forms

Form	Route	Strength
Solution	Oral	50 mg/ml
Capsule	Oral	250 mg/1
Capsule	Oral	250 1/1
Capsule, liquid filled	Oral	250 mg/1
Solution	Oral	250 mg/5mL
Syrup	Oral	5.000 g
Capsule	Oral
Syrup	Oral	50 mg/ml
Capsule	Oral	250 mg
Syrup	Oral	250 MG/5ML
Syrup	Oral	250 mg / 5 mL

Prices

Unit description	Cost	Unit
Ethosuximide 250 mg/5ml Solution 474ml Bottle	84.2USD	bottle
Ethosuximide 250 mg capsule	1.26USD	capsule
Zarontin 250 mg capsule	1.16USD	capsule
Zarontin 250 mg/5ml Solution	0.34USD	ml
Zarontin 50 mg/ml Syrup	0.07USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	64.5 °C	PhysProp
water solubility	39.2 g/L	Not Available
logP	0.38	ATKINSON,HC & BERG,EJ (1988)

Predicted Properties

Property	Value	Source
Water Solubility	101.0 mg/mL	ALOGPS
logP	0.1	ALOGPS
logP	0.55	Chemaxon
logS	-0.15	ALOGPS
pKa (Strongest Acidic)	10.73	Chemaxon
pKa (Strongest Basic)	-6.6	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	2	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	46.17 Å²	Chemaxon
Rotatable Bond Count	1	Chemaxon
Refractivity	35.96 m³·mol^-1	Chemaxon
Polarizability	14.45 Å³	Chemaxon
Number of Rings	1	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9983
Caco-2 permeable	+	0.5262
P-glycoprotein substrate	Non-substrate	0.5832
P-glycoprotein inhibitor I	Non-inhibitor	0.7859
P-glycoprotein inhibitor II	Non-inhibitor	0.9923
Renal organic cation transporter	Non-inhibitor	0.8867
CYP450 2C9 substrate	Non-substrate	0.8492
CYP450 2D6 substrate	Non-substrate	0.9115
CYP450 3A4 substrate	Substrate	0.5108
CYP450 1A2 substrate	Non-inhibitor	0.9242
CYP450 2C9 inhibitor	Non-inhibitor	0.9072
CYP450 2D6 inhibitor	Non-inhibitor	0.9232
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.9276
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.93
Ames test	Non AMES toxic	0.858
Carcinogenicity	Non-carcinogens	0.8526
Biodegradation	Not ready biodegradable	0.9299
Rat acute toxicity	1.9213 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9939
hERG inhibition (predictor II)	Non-inhibitor	0.9795

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (8.34 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
GC-MS Spectrum - EI-B	GC-MS	splash10-08mi-9400000000-44583cdc88d3203a4e84
GC-MS Spectrum - CI-B	GC-MS	splash10-0006-1900000000-1c27ada66f7846f9d155
GC-MS Spectrum - CI-B	GC-MS	splash10-0006-2900000000-19e57defe9ded4ed42b4
Mass Spectrum (Electron Ionization)	MS	splash10-08mi-9300000000-3d87944377ee1f85803d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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insights and accelerate drug research.

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Details1. Voltage-dependent T-type calcium channel subunit alpha-1G

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Scaffold protein binding
Specific Function: 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, hor...
Gene Name: CACNA1G
Uniprot ID: O43497
Uniprot Name: Voltage-dependent T-type calcium channel subunit alpha-1G
Molecular Weight: 262468.62 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E: Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32. [Article]
Wang G, Thompson SM: Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69. doi: 10.1523/JNEUROSCI.3296-08.2008. [Article]
Matthews EA, Dickenson AH: Effects of ethosuximide, a T-type Ca(2+) channel blocker, on dorsal horn neuronal responses in rats. Eur J Pharmacol. 2001 Mar;415(2-3):141-9. [Article]

Enzymes

Details1. Cytochrome P450 3A Subfamily (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:

Name	UniProt ID
Cytochrome P450 3A4	P08684
Cytochrome P450 3A43	Q9HB55
Cytochrome P450 3A5	P20815
Cytochrome P450 3A7	P24462

References

Bachmann K, He Y, Sarver JG, Peng N: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes. Xenobiotica. 2003 Mar;33(3):265-76. doi: 10.1080/0049825021000061606 . [Article]

Details2. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Bachmann K, He Y, Sarver JG, Peng N: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes. Xenobiotica. 2003 Mar;33(3):265-76. doi: 10.1080/0049825021000061606 . [Article]
Sarver JG, Bachmann KA, Zhu D, Klis WA: Ethosuximide is primarily metabolized by CYP3A when incubated with isolated rat liver microsomes. Drug Metab Dispos. 1998 Jan;26(1):78-82. [Article]

Details3. Cytochrome P450 2E1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name: CYP2E1
Uniprot ID: P05181
Uniprot Name: Cytochrome P450 2E1
Molecular Weight: 56848.42 Da

References

Bachmann K, He Y, Sarver JG, Peng N: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes. Xenobiotica. 2003 Mar;33(3):265-76. doi: 10.1080/0049825021000061606 . [Article]

Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:52

Ethosuximide

Identification

Structure for Ethosuximide (DB00593)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References

Enzymes

Components:

References

References

References