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Curr Top Med Chem. 2010;10(2):207-21.

5-HT6 receptor antagonists as potential therapeutics for cognitive impairment.

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Worldwide Discovery Research, Cephalon Inc., West Chester, PA 19380, USA.


Cognitive impairment (CI) has been recognized as a core feature of Alzheimer's disease (AD) and schizophrenia. The 5-HT(6) receptor is an attractive target for the development of cognitive enhancers due to its unique localization and pharmacology. 5-HT(6) receptor antagonists have been shown to modulate multiple neurotransmitter systems and therefore enhance cognition in preclinical studies. This premise translated into the clinical efficacy of the 5-HT(6) receptor antagonist SB-742457 in mild-to-moderate AD patients. Advances in the understanding of the structure-activity-relationship, the design of novel 5-HT(6) receptor ligands and their potential application for the treatment of CI are reviewed.

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