Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment

• DOI: 10.1073/pnas.1410315111
• Publication Date: 2014-08-26T03:20:35Z
• Authors: Cédric Lecoutey; Damien Hedou; Thomas Freret; Patrizia Giannoni; Florence Gaven; Marc Since; Valentine Bouet; Céline Ballandonne; Sophie Corvaisier; Aurélie Malzert F...; Serge Mignani; Thierry Cresteil; Michel Boulouard; Sylvie Claeysen; Christophe Rochais; Patrick Dallemagne
• Keywords: Druggability

Significance Targeting more than one molecular cause implied in the pathogenesis of Alzheimer’s disease (AD) with a sole drug is considered promising challenge, because it may address numerous failures that recently occurred during clinical trials were conducted this area. Donecopride has been designed by us as multitarget-directed ligand, targeting both serotonin subtype 4 receptor and acetylcholinesterase excellent vitro activities. The latter seems able to not only restore cholinergic neurotransmission altered AD but also, promote secretion neurotrophic protein detrimental neurotoxic amyloid-β peptide. With its drugability, donecopride further displayed significant procognitive effects mice generated lead for previously unidentified approach treatment.