Donecopride, a Swiss army knife with potential interest against Alzheimer's disease - Archive ouverte HAL Access content directly
Journal Articles British Journal of Pharmacology Year : 2020

Donecopride, a Swiss army knife with potential interest against Alzheimer's disease

Joël Bockaert
Santiago Rivera


BACKGROUND AND PURPOSE: We recently identified donecopride as a pleiotropic compound able to inhibit acetylcholinesterase and to activate serotonin subtype 4 receptor. The purpose of the present article is to establish its potential therapeutic interest against Alzheimer's disease (AD).EXPERIMENTAL APPROACH: The present work used both in cellulo and in vivo models of AD.KEY RESULTS: In the present study, we show that, in vivo under chronic administration, donecopride displays potent anti-amnesic properties in two different animal models of Alzheimer's disease (AD) (transgenic 5XFAD mice and mice exposed to soluble amyloid-β peptides). Donecopride preserved learning capacities, including working and long-term spatial memories, which were evaluated with various behavioral tests (novel object recognition, Y-maze, Morris water maze). These behavioral observations found molecular correlation with the interactions of donecopride related to the two main types of molecular damage in AD. Indeed, a decrease in amyloid aggregation was observed in the brain of the treated transgenic mice, as well as a reduction in tau hyperphosphorylation in rat primary cultures of hippocampal neurons. At the cellular level, donecopride exerted neuroprotective effects toward neurons and the neurite network, as well as neurotrophic benefits, expressed as the formation of new synapses.CONCLUSIONS & IMPLICATIONS: Pleiotropic donecopride acts like a Swiss army knife, displaying sustainable symptomatic therapeutic effects and potential disease-modifying roles against AD. Clinical trials with this promising drug candidate will soon be undertaken to confirm its therapeutic potential in humans.
Fichier principal
Vignette du fichier
2019 BJP Rochais.pdf (429.81 Ko) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-02428730 , version 1 (17-02-2020)



Christophe Rochais, Cédric Lecoutey, Katia Hamidouche, Patrizia Giannoni, Florence Gaven, et al.. Donecopride, a Swiss army knife with potential interest against Alzheimer's disease. British Journal of Pharmacology, inPress, 177 (9), pp.1988-2005. ⟨10.1111/bph.14964⟩. ⟨hal-02428730⟩
324 View
187 Download



Gmail Facebook Twitter LinkedIn More