Contenido principal del artículo

Ronny Vargas Monge
Universidad de Costa Rica Universidad de Barcelona
España
Jordi Soley Casales
Universidad de Barcelona
España
Vol. 62 Núm. 1 (2021), Artículos de revisión, Páginas 90-111
Recibido: jul 21, 2020 Aceptado: nov 12, 2020 Publicado: dic 20, 2020
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Resumen

Objetivo: Ejecutar una revisión sistemática sobre las estrategias de desarrollo terapéutico para Alzheimer y Esquizofrenia basadas en la modulación alostérica positiva del receptor M1.

Método: Se realizó una búsqueda sistemática de artículos científicos del año 2015 en adelante en PubMed, Ebsco, y Sicence Direct, siguiendo pautas de palabras clave, criterios de inclusión y exclusión establecidas.

Resultados: Un total de 44 artículos cumplieron los criterios establecidos, 20 de ellos son revisiones, y 11 son publicaciones donde se sintetiza uno o más compuestos y se procede a su evaluación farmacológica. La mitad de las publicaciones que realizan una evaluación in vivo corresponden a publicaciones del Centro para el Descubrimiento de Medicamentos en Neurociencias de la Universidad de Vanderbilt. Su principal descubrimiento, el compuesto VU0486846, es el derivado más novedoso de una línea de avances terapéuticos basada en la activación alostérica del receptor M1, que no posee actividad agonista directo pero si es capaz de modular la actividad de la acetilcolina, demostrando ausencia de efectos adversos colinérgicos severos en modelos animales. La búsqueda de derivados de la molécula con balance de propiedades superiores no proporciona un mejor candidato.

Conclusiones: El desarrollo de compuesto VU0486846 corresponde un importante hito en la búsqueda de tratamientos para la enfermedad de Alzheimer y la Esquizofrenia. El éxito de esta molécula y su ruta de investigación, es una validación de la importancia farmacológica de la modulación alostérica en la búsqueda de nuevas dianas farmacológicas.

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