High-potency ligands for DREADD imaging and activation in rodents and monkeys

Nat Commun. 2019 Oct 11;10(1):4627. doi: 10.1038/s41467-019-12236-z.


Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain
  • Clozapine / analogs & derivatives
  • Clozapine / chemistry
  • Designer Drugs*
  • Fluorine Radioisotopes / analysis*
  • HEK293 Cells
  • Haplorhini
  • Humans
  • Ligands
  • Neuroanatomical Tract-Tracing Techniques / methods
  • Neuronal Tract-Tracers / analysis*
  • Neuronal Tract-Tracers / chemistry
  • Positron-Emission Tomography / methods
  • Rodentia


  • Designer Drugs
  • Fluorine Radioisotopes
  • Ligands
  • Neuronal Tract-Tracers
  • Clozapine
  • clozapine N-oxide