Serotonin Receptors of Type 6 (5-HT6): From Neuroscience to Clinical Pharmacology

Donatella      Marazziti; Stefano      Baroni; Franco      Borsini; Michela      Picchetti; Elena      Vatteroni; Valentina      Falaschi; Mario      Catena-Dell’Osso

Abstract

The serotonin (5-HT) receptors of type 6 (5-HT6) are quite different from all other 5-HT receptors, as they include a short third cytoplasmatic loop and a long C-terminal tail, and one intron located in the middle of the third cytoplasmatic loop.

A lot of controversies still exist regarding their binding affinity, effects of 5-HT6 ligands on brain catecholamines, behavioral syndromes regulated by them, and brain distribution.

In spite of the lack of information on metabolic pattern of the various compounds, some of 5-HT6 receptor ligands entered the clinical development as potential anti-dementia, antipsychotic, antidepressant and anti-obese drugs.

The present paper is a comprehensive review on the state of art of the 5-HT6 receptors, while highlighting the potential clinical applications of 5-HT6 receptor agonists/antagonists.

Keywords: Serotonin, serotonin receptors, serotonin receptors of type 6, agonists, antagonists, neurochemistry, distribution, clinical pharmacology