ETHOSUXIMIDE

Description Generic formulation Indications Dose titration Plasma levels monitoring Cautions Interactions Special populations Behavioural and cognitive effects in patients with epilepsy Psychiatric use

Product Name: ETHOSUXIMIDE
CAS No.: 77-67-8
Chemical Name: ETHOSUXIMIDE
Synonyms: Zarontin;h940;H 940;H-490;Pemal;pm671;Suxin;ci366;Etomal;PM 671
CBNumber: CB1420630
Molecular Formula: C7H11NO2
Formula Weight: 141.17
MOL File: 77-67-8.mol

More

Less

ETHOSUXIMIDE Property

Melting point:: 51 °C
Boiling point:: 150 °C / 12mmHg
Density: 1.1522 (rough estimate)
refractive index: 1.5026 (estimate)
storage temp.: 2-8°C
solubility: ethanol: 100 mg/mL
form: Solid
pka: pKa 9.5 (Uncertain)
color: White to Off-White
Water Solubility: 190g/L(25 ºC)
Merck: 14,3748
BCS Class: 1,3
CAS DataBase Reference: 77-67-8

More

Less

Safety

Hazard Codes: Xn,T,F
Risk Statements: 22-39/23/24/25-23/24/25-11
Safety Statements: 36-45-36/37-16-7
WGK Germany: 3
RTECS: WN2800000
HS Code: 2925190100
Hazardous Substances Data: 77-67-8(Hazardous Substances Data)
Toxicity: LD50 in mice (g/kg): 1.65 i.p.; 1.75 orally (Najer)

More

Less

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P501Dispose of contents/container to..…

More

Less

N-Bromosuccinimide Price

Sigma-Aldrich

Product number: 1264002
Product name: Ethosuximide
Purity: United States Pharmacopeia (USP) Reference Standard
Packaging: 500mg
Price: $174.4
Updated: 2024/03/01

Sigma-Aldrich

Product number: BP146
Product name: Ethosuximide
Purity: British Pharmacopoeia (BP) Reference Standard
Packaging: 200MG
Price: $262
Updated: 2023/06/20

Sigma-Aldrich

Product number: 68459
Product name: Ethosuximide
Purity: analytical standard
Packaging: 100mg
Price: $73.5
Updated: 2022/05/15

TCI Chemical

Product number: E0746
Product name: Ethosuximide
Purity: >98.0%(GC)(T)
Packaging: 5g
Price: $45
Updated: 2024/03/01

TCI Chemical

Product number: E0746
Product name: Ethosuximide
Purity: >98.0%(GC)(T)
Packaging: 25g
Price: $129
Updated: 2024/03/01

More

Less

ETHOSUXIMIDE Chemical Properties,Usage,Production

Description

Ethosuximide is a first- generation antiepileptic drug (AED) known under the proprietary brand name of Zarontin® (Pfizer, New York, NY) in the UK and USA.

Generic formulation

MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

It is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns, such as patient anxiety and risk of confusion/ dosing error.

Indications

Epilepsy: monotherapy and adjunctive therapy of absence seizures; adjunctive therapy of generalized tonic- clonic seizures.

Recommendations summarized from NICE (2012)

Seizure types: first line (absence seizures), adjunctive (absence seizures).
Epilepsy types: first line (absence syndromes), adjunctive (absence syndromes).

Dose titration

250 mg bd, then increased in steps of 250 mg every 5– 7 days; usual maintenance 1000– 1500 mg daily, divided into two doses (max. 2000 mg daily).

Plasma levels monitoring

Monitoring ethosuximide plasma levels can be useful in selected cases, although the evidence for a therapeutic plasma range is limited (suggested therapeutic plasma concentrations 40–100 mg/ L) and a toxic limit has not been consistently defined.

Cautions

Patients with acute porphyrias.

Interactions

With AEDs

Plasma concentration of ethosuximide is reduced by the glucuronidation inducers carbamazepine, phenytoin, phenobarbital, and primidone.
Plasma concentration of ethosuximide has been reported to be both increased and decreased by valproate.
Ethosuximide can raise serum levels of phenytoin.

With other drugs
Metabolism of ethosuximide is inhibited by isoniazid, resulting in increased plasma concentration and risk of toxicity.

With alcohol/food
There are no known specific interactions between alcohol and ethosuximide, and there are no specific foods that must be excluded from diet when taking ethosuximide.

Special populations

Hepatic impairment
Use with caution.

Renal impairment
Use with caution.

Pregnancy

The dose of ethosuximide should be monitored carefully during pregnancy and after delivery, and adjustments made on a clinical basis.
Ethosuximide crosses the placenta and cases of birth defects have been reported. Therefore, the prescribing physician should weigh the benefits versus the risks of ethosuximide in treating or counselling epileptic women of childbearing age.
Ethosuximide is excreted in breastmilk and the effects of ethosuximide on the nursing infant are unknown. Therefore, ethosuximide should be used in nursing mothers only if the benefits clearly outweigh the risks and breastfeeding is best avoided.

Behavioural and cognitive effects in patients with epilepsy

Adverse behavioural effects can be of clinical significance, and include the possible induction of anxiety, depression, confusion, irritability, aggression, hallucinations, and intermittent impairment of consciousness These episodes can occur following cessation of seizures and normalization of the electroencephalogram (EEG), and resolve with discontinuation of ethosuximide and seizure recurrence (alternative psychosis in the context of forced normalization). Among first- generation AEDs, ethosuximide is characterized by a relatively favourable cognitive profile, with low incidence of cognitive adverse effects.

Psychiatric use

Ethosuximide as adjunctive treatment of bipolar disorder was found to be ineffective in patients with acute mania. This AED has no approved indications or clinical uses in psychiatry.

Chemical Properties

White to Off-White Solid

Originator

Zarontin,Parke Davis,US,1960

Uses

Ethosuximide is an anticonvulsant drug that is used in minor forms of epilepsy.

Uses

cholinergic

Uses

Anticonvulsant.

Definition

ChEBI: A dicarboximide that is pyrrolidine-2,5-dione in which the hydrogens at position 3 are substituted by one methyl and one ethyl group. An antiepileptic, it is used in the treatment of absence seizures and may be used for myoclonic seizures, but is ineffect ve against tonic-clonic seizures.

Manufacturing Process

α-Ethyl-α-methylsuccinimide is known in the prior art as a chemical entity, having been prepared according to the method described by Sircar, J. Chem. Soc., 128:600 (1927), and characterized in J. Chem. Soc., 128:1254 (1927).
In its manufacture, methyl ethyl ketone is condensed with ethylcyanoacetate to give ethyl-2-cyano-3-methyl-2-pentenoate. That, in turn, adds HCN to give ethyl-2,3-dicyano-3-methyl pentanoate. Saponification and decarboxylation gives 2-methyl-2-ethyl succinonitrile. Heating with aqueous NH3 gives the diamide which loses NH3 and cyclizes to ethosuximide.

brand name

Epileo Petitmal (Eisai), Pemal (Benzon), Petnidan (Desitin Arzneimittel), Suxilep (Parke – Davis, Jenapharm), Suxinutin/Zarontin (Parke – Davis).

Therapeutic Function

Anticonvulsant

Biological Functions

It is now generally accepted that the specific antiepileptic action of ethosuximide (and the older agent trimethadione, no longer employed) against absence epilepsy is its ability to reduce the low-threshold calcium current (LTCC) or T (transient) current. These currents underlie the 3-Hz spike wave discharges that are characteristic of absence epilepsy. A blockade of T-calcium current is likely also to be a mechanism used by valproic acid.
The only clinical use for ethosuximide (Zarontin) is in the treatment of absence epilepsy. If absence attacks are the only seizure disorder present, ethosuximide alone is effective. If other types of epilepsy are present, ethosuximide can be readily combined with other agents.
For the most part, ethosuximide is a safe drug. Most of the side effects are dose related and consist of nausea, gastrointestinal irritation, drowsiness, and anorexia. A variety of blood dyscrasias have been reported, but serious blood disorders are quite rare.

General Description

Ethosuximide is considered the prototypical anticonvulsantneeded for treating patients with absence seizures.Ethosuximide and the N-dealkylated active metabolite ofmethsuximide work by blocking the lowthresholdT-type calcium channels, thereby reducing thehyperexcitability of thalamic neurons that is specifically associatedwith absence seizure.

Biochem/physiol Actions

Ethosuximide is an anticonvulsant drug and an antagonist for T-type calcium channel. It is known to prevent spike wave discharges, characterized in absence seizures.

Clinical Use

Although ethosuximide is the drug of choice for treatment of simple absence seizures, it is not effective against partial complex or tonic-clonic seizures and may increase the frequency of grand mal attacks. Thus, it must be administered in combination with other AEDs when treating persons with mixed seizure types. Ethosuximide is a substrate for both CYP3A4 and CYP2E1. The major metabolite for ethosuximide is 3-(1-hydroxyethyl) succinimide, which is inactive and excreted unconjugated into the urine Several additional metabolites have been characterized recently. Approximately 20% of an oral dose is excreted unchanged.
Although ethosuximide is thought to be the least toxic of the succinimides, it can cause gastrointestinal disturbances and dose-related CNS effects, such as drowsiness, dizziness, ataxia, sleep disturbances and depression. Idiosyncratic hypersensitivity reactions include severe rashes, leukopenia, agranulocytosis (some fatal), systemic lupus erythematosus, and parkinsonian-like symptoms. In addition to being less toxic than trimethadione, ethosuximide offers a wider range of protection against different kinds of absence seizures.

Synthesis

Ethosuximide, 3-ethyl-3-methypyrrolidine-2,5-dione (9.3.4) is synthesized from methylethylketone and cyanoacetic ester, which are condensed in Knoevanagel reaction conditions. Then hydrogen cyanide is added to the resulting product (9.3.1). After acidic hydrolysis and decarboxylation of synthesized dinitrile (9.3.2), 2-methyl-2-ethylsuccinic acid (9.3.3) is formed. Reacting this product with ammonia gives the diammonium salt, and heterocyclization into the ethosuximide (9.3.4) takes place during subsequent heating [8,9].

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: concentration increased by isoniazid
. Antidepressants: lower convulsive threshold; avoid with St John’s wort.
Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenytoin and phenobarbital; concentration of fosphenytoin and phenytoin possibly increased; concentration increased by valproate.
Antimalarials: anticonvulsant effect antagonised by mefloquine.
Antipsychotics: lower convulsive threshold.
Orlistat: possible increased risk of convulsions.

Metabolism

Ethosuximide is extensively hydroxylated in the liver to its principal metabolite which is reported to be inactive. Ethosuximide is excreted in the urine mainly in the form of its metabolites, either free or conjugated, but about 12-20% is also excreted unchanged.

ETHOSUXIMIDE Preparation Products And Raw materials

Raw materials

1-ETHYL-1-METHYLSUCCINIC ACID

Preparation Products

More

Less

ETHOSUXIMIDE Suppliers

Americas 1 Belgium 1 Canada 4 China 105 Europe 1 France 2 Germany 4 India 8 Japan 2 Poland 1 Slovakia 1 Switzerland 1 The Netherlands 3 United Kingdom 7 United States 31 Venezuela 1 Global 173

TargetMol Chemicals Inc.

Tel: +1-781-999-5354 +1-00000000000
Email: marketing@targetmol.com
Country: United States
ProdList: 32165
Advantage: 58

TargetMol Chemicals Inc.

Tel: +8613564774135
Email: zijue.cai@tsbiochem.com
Country: United States
ProdList: 19885
Advantage: 58

TargetMol Chemicals Inc.

Tel
Email: support@targetmol.com
Country: United States
ProdList: 38632
Advantage: 58

Aladdin Scientific

Tel: +1-+1(833)-552-7181
Email: sales@aladdinsci.com
Country: United States
ProdList: 57505
Advantage: 58

Alfa Chemistry

Tel
Email: info@alfa-chemistry.com
Country: United States
ProdList: 2344
Advantage: 58

Cayman Chemical Company

Tel: --
Fax: --
Email: cayman@caymanchem.com
Country: United States
ProdList: 6213
Advantage: 81

Crescent Chemical Company

Tel: --
Fax: --
Email: fran@creschem.com
Country: United States
ProdList: 1441
Advantage: 58

Parchem Fine & Specialty Chemicals

Tel: --
Fax: --
Email: info@parchem.com
Country: United States
ProdList: 1031
Advantage: 58

Selleck Chemicals LLC

Tel: --
Fax: --
Email: sales@selleckchem.com
Country: United States
ProdList: 1848
Advantage: 58

TCI America, Inc. (Tokyo Chemical Industry Co., Ltd.)

Tel: --
Fax: --
Email: .Crew@tcichemicals.com
Country: United States
ProdList: 3164
Advantage: 58

MilliporeSigma (Sigma-Aldrich Corp.)

Tel: --
Fax: --
Email: @sial.com
Country: United States
ProdList: 5414
Advantage: 58

vulcanchem

Tel: --
Fax: --
Email: info@vulcanchem.com
Country: United States
ProdList: 268
Advantage: 58

CHEMWERTH INC

Tel: --
Fax: --
Email: sales@chemwerth.com
Country: United States
ProdList: 56
Advantage: 58

MedKoo Biosciences, Inc.

Tel: --
Fax: --
Email: sales@medkoo.com
Country: United States
ProdList: 126
Advantage: 58

MuseChem (A division of Adv Biolabs, Inc.)

Tel: --
Fax: --
Email: @musechem.com
Country: United States
ProdList: 246
Advantage: 58

Glixx Laboratories Inc.

Tel: --
Fax: --
Email: sales@glixxlabs.com
Country: United States
ProdList: 30
Advantage: 58

RIA International LLC

Tel: --
Fax: --
Email: marketing@riausa.net
Country: United States
ProdList: 1324
Advantage: 50

VWR International, LLC.

Tel: --
Fax: --
Email: @sargentwelch.com
Country: United States
ProdList: 6262
Advantage: 58

Spectrum Chemical Mfg. Corp.

Tel: --
Fax: --
Email: marketing@spectrumchemical.com
Country: United States
ProdList: 3113
Advantage: 60

HBCChem Inc.

Tel: --
Fax: --
Email: sales@hbcchem-inc.com
Country: United States
ProdList: 4569
Advantage: 30

United States Biological

Tel: --
Fax: --
Email: chemicals@usbio.net
Country: United States
ProdList: 6214
Advantage: 80

MedChemExpress

Tel: --
Fax: --
Email: sales@medchemexpress.com
Country: United States
ProdList: 6398
Advantage: 58

Riedel-de Haen AG

Tel: --
Fax: --
Country: United States
ProdList: 6773
Advantage: 87

TCI America

Tel: --
Fax: --
Email: sales@tciamerica.com
Country: United States
ProdList: 6909
Advantage: 75

Waterstone Technology, LLC

Tel: --
Fax: --
Email: sales@waterstonetech.com
Country: United States
ProdList: 6786
Advantage: 30

Generichem Corporation

Tel: --
Fax: --
Email: info@generichem.com
Country: United States
ProdList: 80
Advantage: 60

Advance Scientific & Chemical

Tel: --
Fax: --
Email: sales@advance-scientific.com
Country: United States
ProdList: 6419
Advantage: 71

Sciencelab.com, Inc.

Tel: --
Fax: --
Email: accounting@sciencelab.com
Country: United States
ProdList: 4159
Advantage: 82

ASDI Incorporated

Tel: --
Fax: --
Email: customerservice@asdi.net
Country: United States
ProdList: 6922
Advantage: 67

Spectrum Chemicals & Laboratory Products

Tel: --
Fax: --
Email: sales@spectrumchemical.com
Country: United States
ProdList: 6699
Advantage: 77

Alltech Associates, Inc.

Tel: --
Fax: --
Email: alltech@alltechemail.com
Country: United States
ProdList: 419
Advantage: 60

More

Less

View Lastest Price from ETHOSUXIMIDE manufacturers

Career Henan Chemical Co

Product: Ethosuximide 77-67-8
Price: US $1.00/KG
Min. Order: 1KG
Purity: ≥98%
Supply Ability: 20 tons
Release date: 2020-01-09

77-67-8, ETHOSUXIMIDERelated Search:

ALPHA-METHYL-ALPHA-PROPYLSUCCINIMIDE ETHOSUXIMIDE Roxoperone Succinimide ETHOSUXIMIDE IMPURITY A 6-azaspiro[3.4]octane-5,7-dione 2-AZASPIRO[4.5]DECANE-1,3-DIONE ETHOSUXIMIDE ASSAY STANDARD BP(CRM STANDARD) ETHOSUXIMIDE BP STANDARD(CRM STANDARD) ETHOSUXIMIDE WHO(CRM STANDARD) ETHOSUXIMIDE USP(CRM STANDARD) ANTI-ETHOSUXIMIDE N-(benzyloxy)-2-azaspiro(4.4)nonane-1,3-dione 3-CHLORO-4-(1,3-DIOXO-2-AZASPIRO[4.4]NON-2-YL)BENZENESULFONYL CHLORIDE PB 382 N-hydroxycantharidinimide RS 86 (R)-(-)-Ethosuximide,(R)-Ethosuximide

Succinimide, 2-ethyl-2-methyl- (6CI, 7CI, 8CI)

α-Ethyl-α-methylsuccinimide

α-Methyl-α-ethylsuccinimide

3-ethyl-3-methyl-pyrrolidine-2,5-quinone

EthosuxiMide, USP

Ethosuximide (500 mg)

3-Ethyl-3-Methyl-

Ethosuximide solution

ETHOSUXIMIDE

3-Ethyl-3-methyl-2,5-pyrrolidinedione

3-ethyl-3-methyl-2,5-pyrrolidine-dione

2-ETHYL-2-METHYLSUCCINIMIDE

2,5-Pyrrolidinedione, 3-ethyl-3-methyl-

2-ethyl-2-methyl-succinimid

Ethosuccimide

Ethosuccinimide

Ethosuxide

Ethymal

Etomal

Etosuximid

Etosuximida

gamma-Methyl-gamma-ethylsuccinimide

gamma-methyl-gamma-ethyl-succinimide

H 940

H-490

h940

Mesentol

NSC-64013

Pemal

Pemalin

Pentinimid

Peptinimid

Petinimid

Petnidan

Piknolepsin

PM 671

pm671

Pyknolepsinum

Ronton

Simatin

Simatin(E)

Succimal

Succimitin

Succinimide, 2-ethyl-2-methyl-

Suxilep

Suximal

Suxin

Suxinutin

Thetamid

2-Methyl-2-ethylsuccinimide

3-Methyl-3-ethylsuccinimide

(RS)-3-ETHYL-3-METHYL-PYRROLIDINE-2,5-DIONE

3-ethyl-3-methyl-5-pyrrolidinedione

3-Ethyl-3-methylpyrrolidine-2,5-dione

3-Ethyl-3-methylpyrroline-2,5-dione

3-ethyl-3-methylsuccinimide

3-Methyl-3-ethylpyrrolidine-2,5-dione

Aethosuximide