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丙戊酸盐诱导的抗惊厥作用、致畸性和肝毒性之间的差异。物种差异、药代动力学、代谢方面以及结构特异性对开发替代抗癫痫药物(如δ2-丙戊酸盐)的影响。

Differentiation between valproate-induced anticonvulsant effect, teratogenicity and hepatotoxicity. Aspects of species variation, pharmacokinetics, metabolism and implications of structural specificity for the development of alternative antiepileptic agents such as delta 2-valproate.

作者信息

Nau H, Siemes H

机构信息

Institute of Toxicology and Embryopharmacology, Free University Berlin, Germany.

出版信息

Pharm Weekbl Sci. 1992 Jun 19;14(3A):101-7. doi: 10.1007/BF01962697.

Abstract

Valproate is metabolized into a large number of compounds via various metabolic routes. Metabolic profiles depend on species and age. Hepatotoxicity may be correlated with abnormal metabolism, especially in young age. Teratogenicity is associated with specific structural requirements: a free carboxyl atom connected to a carbon atom which also carries a hydrogen, and two carbon chains. This provides a clue for the development of alternative antiepileptic agents.

摘要

丙戊酸盐通过多种代谢途径代谢为大量化合物。代谢谱取决于物种和年龄。肝毒性可能与代谢异常相关,尤其是在幼年时期。致畸性与特定的结构要求有关:一个与也带有氢原子的碳原子相连的游离羧基,以及两条碳链。这为开发替代抗癫痫药物提供了线索。

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