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

Nature communications | 2019

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.

Pubmed ID: 31604917 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: R21 AG054802
  • Agency: NIMH NIH HHS, United States
    Id: ZIA MH002795
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA), International
    Id: ZIA000069
  • Agency: NIMH NIH HHS, United States
    Id: ZIA MH002793

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