We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders

ChemMedChem. 2015 Dec;10(12):1963-7. doi: 10.1002/cmdc.201500437. Epub 2015 Oct 28.

Abstract

The serotonin 2C (5-HT2C ) receptor has been identified as a potential drug target for the treatment of a variety of central nervous system (CNS) disorders, such as obesity, substance abuse, and schizophrenia. In this Viewpoint article, recent progress in developing selective 5-HT2C agonists for use in treating these disorders is summarized, including the work of our group. Challenges in this field and the possible future directions are described. Homology modeling as a method to predict the binding modes of 5-HT2C ligands to the receptor is also discussed. Compared to known ligands, the improved pharmacological profiles of the 2-phenylcyclopropylmethylamine-based 5-HT2C agonists make them preferred candidates for further studies.

Keywords: drug discovery; medicinal chemistry; receptors; schizophrenia; serotonin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amines / chemistry*
  • Amines / therapeutic use
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / pathology
  • Humans
  • Receptor, Serotonin, 5-HT2C / chemistry*
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Serotonin 5-HT2 Receptor Agonists / chemistry*
  • Serotonin 5-HT2 Receptor Agonists / therapeutic use
  • Small Molecule Libraries / chemistry
  • Structure-Activity Relationship

Substances

  • Amines
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • Small Molecule Libraries