Objectives Drug repositioning, that is, the use of a drug in an indication other than the one for which it was initially marketed, is a growing trend. Its origins lie mainly in the attrition experienced in recent years in the field of new drug discovery.

No abstract

In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in mice. The latter displayed procognitive and antiamnesic effects and enhanced sAPPα release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimer's disease.