Liver says no: the ongoing search for safe catechol O-methyltransferase inhibitors to replace tolcapone

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Silva, TB (Autor) Outra; Fernanda Borges (Autor) FCUP; Maria Paula Serrão (Autor) FMUP; Soares da Silva, P (Autor) Outra

Revista

Título: Drug Discovery Today

Vol. 25

Páginas: 1846-1854

ISSN: 1359-6446

Editora: Elsevier

Indexação

ISI Web of Knowledge - 3 Citações

Scopus - 3 Citações

Outras Informações

ID Authenticus: P-00S-MV1

DOI: 10.1016/j.drudis.2020.07.015

Abstract (EN): Catechol O-methyltransferase (COMT) inhibitors are valuable co-adjuvant drugs in the clinical management of Parkinson's disease (PD), and recent data also suggest therapeutic benefits in other neurological disorders associated with dopamine depletion. However, the relationship between tolcapone administration with fatal cases of drug-induced liver damage gave COMT inhibitors a bad reputation as hepatotoxic drugs. Thus, there is a pressing need to feed the pipeline with safe COMT inhibitors to replace tolcapone, the only currently available COMT inhibitor that effectively reaches the brain. Recent efforts led to promising phenolic and nonphenolic COMT inhibitors, which allow isoform-specific targeting and avoid the toxicological and pharmacokinetic (PK) shortcomings of classic nitrocatechols. Here, we describe advances made in this field over the past 5 years.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9