Ethosuximid

Bezeichnung:Ethosuximid

CAS-Nr77-67-8

Englisch Name:ETHOSUXIMIDE

CBNumberCB1420630

SummenformelC7H11NO2

Molgewicht141.17

MOL-Datei77-67-8.mol

Synonyma

Ethosuximid

Ethosuximid physikalisch-chemischer Eigenschaften

Schmelzpunkt	51 °C
Siedepunkt	150 °C / 12mmHg
Dichte	1.1522 (rough estimate)
Brechungsindex	1.5026 (estimate)
storage temp.	2-8°C
Löslichkeit	ethanol: 100 mg/mL
pka	pKa 9.5 (Uncertain)
Aggregatzustand	Solid
Farbe	White to Off-White
Wasserlöslichkeit	190g/L(25 ºC)
Merck	14,3748
BCS Class	1,3
CAS Datenbank	77-67-8

Sicherheit

Kennzeichnung gefährlicher	Xn,T,F
R-Sätze:	22-39/23/24/25-23/24/25-11
S-Sätze:	36-45-36/37-16-7
WGK Germany	3
RTECS-Nr.	WN2800000
HS Code	2925190100
Giftige Stoffe Daten	77-67-8(Hazardous Substances Data)
Toxizität	LD50 in mice (g/kg): 1.65 i.p.; 1.75 orally (Najer)

Gefahreninformationscode (GHS)

ETHOSUXIMIDE Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
S-Sätze Betriebsanweisung:
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Chemische Eigenschaften
White to Off-White Solid
Originator
Zarontin,Parke Davis,US,1960
Verwenden
cholinergic
Verwenden
Anticonvulsant.
Verwenden
Ethosuximide is an anticonvulsant drug that is used in minor forms of epilepsy.
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.
Trademarks
Epileo Petitmal (Eisai), Pemal (Benzon), Petnidan (Desitin Arzneimittel), Suxilep (Parke – Davis, Jenapharm), Suxinutin/Zarontin (Parke – Davis).
Therapeutic Function
Anticonvulsant
Biologische Funktion
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.
Allgemeine Beschreibung
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.
Synthese
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].
Arzneimittelwechselwirkung
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.
Stoffwechsel
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 Upstream-Materialien And Downstream Produkte

Ethosuximid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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