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.
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.
Nau
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H
Institute of Toxicology and Embryopharmacology, Free University Berlin, Germany.
Siemes
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H
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000375:Aging / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics
D000927:Anticonvulsants; D014635:Valproic Acid