5‐HT6 antagonists as potential treatment for cognitive dysfunction

Among the potential therapeutic targets for the development of cognitive enhancers for AD and schizophrenia, the 5-HT6 receptor is of especial interest based on its localization, pharmacology, and recent behavioral data showing that 5-HT6 receptor blockade improves cognition in a number of rodent behavioral models. It is localized almost exclusively in the CNS, in areas important for learning and memory, while atypical antipsychotics and tricyclic antidepressants bind with high affinity to this target. 5-HT6 receptor antagonism enhances neurotransmission at cholinergic and glutamatergic neurons, as well as in other pathways. 5-HT6 antagonist medicinal chemistry and potential therapeutic applications for treatment of cognitive dysfunction is broadly reviewed. Drug Dev Res 70, 2009 © 2009 Wiley-Liss, Inc.