Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development.

Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development. Curr Top Med Chem. 2019 Jul 08;: Authors: Wold EA, Wild CT, Cunningham KA, Zhou J Abstract The serotonin (5-HT) 5-HT2C receptor (5-HT2CR) is recognized as a critical mediator of disease-related pathways and behaviors based upon actions in the central nervous system (CNS). Since the 5-HT2CR is a class A G protein-coupled receptor (GPCR), drug discovery efforts have traditionally pursued activation of the receptor through synthetic ligands with agonists proposed for treatment of obesity, substance use disorders and impulse control disorders while antagonists may add value in the treatment of anxiety, depression and schizophrenia. The most significant agonist discovery to date is the FDA-approved anti-obesity medication lorcaserin. In recent years, efforts towards developing other mechanisms to enhance receptor function have resulted in the discovery of positive allosteric modulators (PAMs) for the 5-HT2CR, with several molecule series now reported. The biological significance and context for signaling and function of the 5-HT2CR, and the current status of 5-HT2CR agonists and PAMs are discussed in this review. PMID: 31288724 [PubMed - as supplied by publisher]
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research