Cognitive impairment (CI) has been recognized as a core feature of Alzheimers disease (AD) and schizophrenia. The 5-HT6 receptor is an attractive target for the development of cognitive enhancers due to its unique localization and pharmacology. 5-HT6 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- HT6 receptor antagonist SB-742457 in mild-to-moderate AD patients. Advances in the understanding of the structureactivity- relationship, the design of novel 5-HT6 receptor ligands and their potential application for the treatment of CI are reviewed.
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Rossé et al. (2010) studied this question.
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