In Vitro Metabolism Evaluation of the Ergot Alkaloid Dihydroergotamine: Application of Microsomal and Biomimetic Oxidative Model

Autor(es)

Bauermeister, Anelize ; Aguiar, Fernando Armani ; Mauriz Marques, Lucas Maciel ; Malta, Jr., Jose Dos Santos ; Barros, Fabio ; Callejon, Daniel Roberto ; Moraes de Oliveira, Anderson Rodrigo ; Lopes, Norberto Peporine

• Tipo de documento: Artigo Científico
• Fonte: Planta Medica; v. 82, n. 15, p. 1368-1373, OCT 2016.
• Citações Web of Science: 2

Resumo

Dihydroergotamine is a semisynthetic natural product derived from ergotamine, an ergot alkaloid. It is used to treat migraines, a neurological disease characterized by recurrent moderate to severe headaches. In this work, the in vitro metabolism of dihydroergotamine was evaluated in a biomimetic phase I reaction, aiming to verify all possible formed metabolites. Dihydroergotamine was submitted to an in vitro metabolism assay using rat liver microsomes, and the metabolites were analyzed by HPLC-MS/MS. The biomimetic reactions were performed with Jacobsen catalyst for scaling up production of oxidized metabolites. Two hydroxylated metabolites were isolated and characterized by MS/MS and H-1 NMR analysis. (AU)

• Processo FAPESP: 13/16496-5 - Avaliação do metabolismo in vitro, in vivo e do perfil farmacocinético do alcalóide govaniadina
• Beneficiário: Lucas Maciel Mauriz Marques
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/50265-3 - Metabolismo e distribuição de xenobióticos naturais e sintéticos: da compreensão dos processos reacionais à geração de imagens teciduais
• Beneficiário: Norberto Peporine Lopes
• Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático