Modulación Alostérica Positiva selectiva para el receptor muscarínico M1: descubrimiento y desarrollo del compuesto VU0486846 y su importancia para el desarrollo de tratamientos para el Alzheimer y la Esquizofrenia

Autores/as

  • Ronny Vargas Monge Universidad de Costa Rica Universidad de Barcelona
  • Jordi Soley Casales Universidad de Barcelona

Palabras clave:

Receptor Muscarínico M1, Modulación Alostérica, Alzheimer, Esquizofrenia, Descubrimiento de fármacos

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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Citas

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2020-12-20

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1.
Vargas Monge R, Soley Casales J. Modulación Alostérica Positiva selectiva para el receptor muscarínico M1: descubrimiento y desarrollo del compuesto VU0486846 y su importancia para el desarrollo de tratamientos para el Alzheimer y la Esquizofrenia. Ars Pharm [Internet]. 20 de diciembre de 2020 [citado 20 de abril de 2024];62(1):90-111. Disponible en: https://revistaseug.ugr.es/index.php/ars/article/view/15704

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Vol. 62 Núm. 1 (2021)

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