Ethosuximide
Identification
- Summary
Ethosuximide is an anticonvulsant used to treat petit mal seizures.
- Brand Names
- Zarontin
- Generic Name
- Ethosuximide
- DrugBank Accession Number
- DB00593
- Background
An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Ethosuximide (DB00593)
- Weight
- Average: 141.1677
Monoisotopic: 141.078978601 - Chemical Formula
- C7H11NO2
- Synonyms
- (±)-2-ethyl-2-methylsuccinimide
- 2-ethyl-2-methylsuccinimide
- 2-methyl-2-ethylsuccinimide
- 3-ethyl-3-methyl-2,5-pyrrolidinedione
- 3-ethyl-3-methylsuccinimide
- 3-methyl-3-ethylpyrrolidine-2,5-dione
- 3-methyl-3-ethylsuccinimide
- Aethosuximide
- Atysmal
- Ethosuximid
- Ethosuximide
- éthosuximide
- Ethosuximidum
- Etosuximida
- Thilopemal
- α-ethyl-α-methylsuccinimide
- α-methyl-α-ethylsuccinimide
- γ-ethyl-γ-methyl-succinimide
- γ-methyl-γ-ethyl-succinimide
- External IDs
- CI-366
- CN-10,395
- CN-10395
- PM-671
Pharmacology
- Indication
For the treatment of petit mal epilepsy.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
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 inhibitorHumans - 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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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 Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects 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. Abiraterone The metabolism of Ethosuximide can be decreased when combined with Abiraterone. 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 adverse effects can be increased when Ethosuximide is combined with Acetazolamide. 
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- Avoid alcohol.
- Take with food.
Products
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- 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 Region Image Zarontin Capsule 250 mg/1 Oral Parke Davis Div Of Pfizer Inc 2000-09-22 Not applicable US 
Zarontin Cap 250mg Capsule 250 mg Oral Erfa Canada 2012 Inc 1960-12-31 Not applicable Canada 
Zarontin Syr 250mg/5ml Syrup 250 mg / 5 mL Oral Erfa Canada 2012 Inc 1964-12-31 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ethosuximide Capsule, liquid filled 250 mg/1 Oral bryant ranch prepack 2016-10-21 Not applicable US Ethosuximide Capsule 250 1/1 Oral Zydus Pharmaceuticals Usa, Inc. 2012-10-10 Not applicable US Ethosuximide Solution 250 mg/5mL Oral Mikart, LLC 2003-12-22 Not applicable US Ethosuximide Solution 250 mg/5mL Oral Pharmaceutical Associates, Inc. 2000-11-22 Not applicable US Ethosuximide Capsule, liquid filled 250 mg/1 Oral Bionpharma Inc. 2016-10-21 Not applicable US Ethosuximide Capsule 250 mg/1 Oral Greenstone LLC 2015-10-12 Not applicable US Ethosuximide Capsule 250 mg/1 Oral Teva 2002-11-01 2017-04-30 US 
Ethosuximide Capsule 250 mg/1 Oral Strides Pharma Science Limited 2019-05-15 Not applicable US Ethosuximide Solution 250 mg/5mL Oral VersaPharm Incorporated 2004-01-01 Not applicable US Ethosuximide Capsule 250 mg/1 Oral bryant ranch prepack 2019-05-15 Not applicable US
Categories
- ATC Codes
- N03AD01 — EthosuximideN03AD51 — Ethosuximide, combinations
- Drug Categories
- Agents causing hyperkalemia
- Anti-epileptic Agent
- Antiarrhythmic agents
- Anticonvulsants
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Decreased Central Nervous System Disorganized Electrical Activity
- Imides
- Nervous System
- Potential QTc-Prolonging Agents
- Pyrrolidines
- Pyrrolidinones
- QTc Prolonging Agents
- Succinimide Derivatives
- Succinimides
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrrolidine-2-ones. These are pyrrolidines which bear a C=O group at position 2 of the pyrrolidine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrrolidines
- Sub Class
- Pyrrolidones
- Direct Parent
- Pyrrolidine-2-ones
- Alternative Parents
- N-unsubstituted carboxylic acid imides / Dicarboximides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- 2-pyrrolidone / Aliphatic heteromonocyclic compound / Azacycle / Carbonyl group / Carboxylic acid derivative / Carboxylic acid imide / Carboxylic acid imide, n-unsubstituted / Dicarboximide / Hydrocarbon derivative / Lactam
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- pyrrolidinone, dicarboximide (CHEBI:4887)
- Affected organisms
- Humans and other mammals
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
- 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 Epilepsy, Absence / Ketogenic Dieting 1 3 Recruiting Treatment Irritable Bowel Syndrome (IBS) 1 2 Completed Supportive Care Malignancies / 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 2 Unknown Status Treatment Irritable Bowel Syndrome (IBS) 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 Capsule Oral Solution Oral Capsule Oral 250 mg/1 Capsule Oral 250 1/1 Capsule, liquid filled Oral 250 mg/1 Solution Oral 250 mg/5mL Syrup Oral 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
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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- 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
- 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]
- 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]
- 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]
Drug created on June 13, 2005 13:24 / Updated on September 18, 2021 03:33