Serotonin receptors of type 6 (5-HT6): what can we expect from them?

The serotonin (5-HT) receptors of type 6 (5-HT6) are relatively new. They are quite different from all other 5-HT receptors, as they are characterized by a short third cytoplasmatic loop and a long C-terminal tail, and contain one intron located in the middle of the third cytoplasmatic loop. After some initial controversies, the available findings are now apparently more congruent. Nevertheless, discrepancies still exist, such as those in binding affinity, effects of 5-HT6 ligands on brain catecholamines and behavioral syndromes mediated by them. Much interest in 5-HT6 receptors was triggered by the evidence that some antipsychotics could bind to them. Subsequently, despite the lack of complete information on metabolic patterns of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic and anti-obese drugs. In any case, the available information on both the pharmacology of 5-HT6 receptors is still quite scant. Therefore, with the present paper we aimed at reporting a comprehensive review on the status of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.