Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors

V. J. Aloyo, K. A. Berg, U. Spampinato, W. P. Clarke, J. A. Harvey

Research output: Contribution to journalReview article

90 Scopus citations

Abstract

Contemporary receptor theory was developed to account for the existence of constitutive activity, as defined by the presence of receptor signaling in the absence of any ligand. Thus, ligands acting at a constitutively active receptor, can act as agonists, antagonists, and inverse agonists. In vitro studies have also revealed the complexity of ligand/receptor interactions including agonist-directed stimulus trafficking, a finding that has led to multi-active state models of receptor function. Studies with a variety of cell types have established that the serotonin 5-HT2A and 5-HT2C receptors also demonstrate constitutive activity and inverse agonism. However, until recently, there has been no evidence to suggest that these receptors also demonstrate constitutive activity and hence reveal inverse agonist properties of ligands in vivo. This paper describes our current knowledge of constitutive activity in vitro and then examines the evidence for constitutive activity in vivo. Both the serotonin 5-HT2A and 5-HT2C receptors are involved in a number of physiological and behavioral functions and are the targets for treatment of schizophrenia, anxiety, weight control, Parkinsonism, and other disorders. The existence of constitutive activity at these receptors in vivo, along with the possibility of inverse agonism, provides new avenues for drug development.

Original languageEnglish (US)
Pages (from-to)160-173
Number of pages14
JournalPharmacology and Therapeutics
Volume121
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • Constitutive activity
  • Inverse agonism
  • Serotonin 5-HT receptor
  • Serotonin 5-HT receptor
  • Stimulus trafficking

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Current status of inverse agonism at serotonin<sub>2A</sub> (5-HT<sub>2A</sub>) and 5-HT<sub>2C</sub> receptors'. Together they form a unique fingerprint.

  • Cite this