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The serotonin 5-HT4 receptor (5-HT4R) is a member of the seven transmembrane-spanning G-protein-coupled receptor (GPCR) family. Since its discovery in mouse colliculi neurons, the 5-HT4R has received a considerable attention for its physiological effect in the central nervous system (CNS). Thanks to the availability of selective 5-HT4 ligands and the cloning of 5-HT4 receptor C-terminal splice variants, many studies have shown the involvement of the 5-HT4R in cognitive processes making this GPCR as a possible therapeutic target for symptomatic treatment of memory disorders such as Alzheimer's disease (AD). After an introduction to the chemistry of 5-HT4R ligands, and the molecular identification and pharmacological characterization of recombinant 5-HT4R, here we discuss on the potential use of 5-HT4R agonists as therapeutical agents influencing the cholinergic system and the amyloid precursor protein processing for the treatment of AD.

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