Targeting the Serotonin 5-HT(7) Receptor in the Search for Treatments for CNS Disorders: Rationale and Progress to Date

The 5-HT(7) (5-hydroxytryptamine 7, serotonin 7) receptor is one of the most recently identified members of the serotonin receptor family. Pharmacological tools, including selective antagonists and, more recently, agonists, along with 5-HT(7) receptor (5-HT(7)R) knock-out mice have revealed the involvement of this receptor in central nervous system processes. Its well-established role in controlling body temperature and regulating sleep and circadian rhythms has implicated this receptor in mood disorders. Thus, the 5-HT(7)R has gained much attention as a possible target for the treatment of depression. Although preclinical data support the antidepressant-like actions of 5-HT(7)R antagonists, their clinical efficacy has not been yet established. Other evidence has implicated the 5-HT(7)R in learning and memory. Preclinical findings suggest that blockade of this receptor may be beneficial against schizophrenia-like cognitive deficits. Other possible indications include nociception, epilepsy, migraine, autism spectrum disorders, and Rett Syndrome. However, the question is whether the beneficial effects may be achieved by activation or blockade of 5-HT(7)Rs. Hence, this review briefly summarises the recent findings on the role of 5-HT(7)Rs and their ligands in CNS disorders.