ETHOSUXIMIDE

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ETHOSUXIMIDE 화학적 특성, 용도, 생산

• 화학적 성질

  White to Off-White Solid

• 용도

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

• 정의

  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.

• 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.

• 일반 설명

  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.

• 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.

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