Detalle Publicación

ARTÍCULO
Impact of neurodegenerative diseases on drug binding to brain tissues: from animal models to human samples
Autores: Ugarte, A.; Corbacho, D.; Aymerich Soler, Marisol; García Osta, Ana María; Cuadrado Tejedor, María del Mar; Oyarzabal, J. (Autor de correspondencia)
Título de la revista: NEUROTHERAPEUTICS
ISSN: 1933-7213
Volumen: 15
Número: 3
Páginas: 742 - 750
Fecha de publicación: 2018
Lugar: WOS
Resumen:
Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.