Novel designer receptors to probe GPCR signaling and physiology

Trends Pharmacol Sci. 2013 Jul;34(7):385-92. doi: 10.1016/ Epub 2013 Jun 13.


Muscarinic receptor-based designer receptors have emerged as powerful novel tools to study G-protein-coupled receptor (GPCR) signaling and physiology. These new designer GPCRs, which are most frequently referred to as DREADDs (designer receptors exclusively activated by designer drug), are unable to bind acetylcholine, the endogenous muscarinic receptor agonist, but can be activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound, with high potency and efficacy. The various DREADDs differ primarily in their G protein coupling preference. More recently, an arrestin-biased DREADD has also been developed. The expression of DREADDs in distinct tissues or cell types has enabled researchers to study the outcome of selective stimulation of distinct GPCR (or arrestin) signaling pathways in a temporally and spatially controlled fashion in vivo. In this review, we provide an up-to-date snapshot of where this field currently stands and which important novel insights have been gained using this new technology.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Ligands
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / metabolism
  • Membrane Transport Modulators / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Protein Conformation
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship


  • Ligands
  • Membrane Transport Modulators
  • Receptors, G-Protein-Coupled