Targeting the 5-ht2c receptor in biological context and the current state of 5-ht2c receptor ligand development

Eric A. Wold, Christopher T. Wild, Kathryn A. Cunningham, Jia Zhou

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


Serotonin (5-HT) 5-HT2C receptor (5-HT2C R) is recognized as a critical mediator of disease-related pathways and behaviors based upon actions in the central nervous system (CNS). Since 5-HT2C R is a class A G protein-coupled receptor (GPCR), drug discovery efforts have traditionally pursued the activation of the receptor through synthetic ligands with agonists proposed for the treatment of obesity, substance use disorders and impulse control disorders while antagonists may add value for 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-HT2C R, with several molecule series now reported. The biological significance and context for signaling and function of the 5-HT2C R, and the current status of 5-HT2C R agonists and PAMs are discussed in this review.

Original languageEnglish (US)
Pages (from-to)1381-1398
Number of pages18
JournalCurrent topics in medicinal chemistry
Issue number16
StatePublished - 2019


  • 5-HT receptor
  • Agonists
  • Allosteric modulation
  • Central nervous system disorders
  • Drug discovery
  • Ligand development
  • Neurotherapeutics
  • Pharmacological probes
  • Positive allosteric modulators
  • Signaling bias
  • Target selectivity

ASJC Scopus subject areas

  • Drug Discovery


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