Зипрасидон

Химические свойства

Tan Solid

Использование

Labelled Ziprasidone, which is used as an antipsychotic. Combined serotonin (5HT2) and dopamine (D2) receptor antagonist.

Определение

ChEBI: A piperazine compound having 1,2-benzothiazol-3-yl- and 2-(6-chloro-1,3-dihydro-2-oxindol-5-yl)ethyl substituents attached to the nitrogen atoms.

Биологические функции

"Ziprasidone is chemically similar to risperidone but with a substitution of piperzinyl and benzisothiazole for piperidinyl and benzisoxazole and with minor aromatic modification. Like risperidone, ziprasidone is a high-affinity antagonist at 5-HT2A/C and D2 receptors as well as at adrenergic α1/α2 and histamine H1 receptors. Moreover, ziprasidone can activate 5-HT1A receptors that regulate dopaminergic neurotransmission in brain regions involved in critical cognitive functions. Thus, in addition to D2 partial agonism, 5-HT1A agonism is now thought to be an important pharmacological property for atypical antipsychotic drug efficacy.

Общее описание

Ziprasidone (Geodon, a benzisothiazolpiprazinylindolonederivative) also has the structuralfeatures of a hybrid molecule between a butyrophenone antipsychoticand a trazodone-like antidepressant. It is highlymetabolized to four major metabolites, only one of which, Smethyldihydroziprasidone,likely contributes to its clinical activity. In humans, less than 5% of the dose isexcreted unchanged. Reduction by aldehyde oxidase accountsfor about 66% of ziprasidone metabolism; two oxidative pathwaysinvolving hepatic CYP3A4 account for the remainder.

Механизм действия

Ziprasidone (half-life, 6 hours) has an oral bioavailability of approximately 60%, which can be enhanced in the presence of fatty foods. It is extensively metabolized (<5% excreted unchanged) by aldehyde oxidase, which results in reductive cleavage of the S–N bond, and then by S-methylation. Ziprasidone also can undergo CYP3A4-catalyzed N-dealkylation and S-oxidation.