High-potency ligands for DREADD imaging and activation in rodents and monkeys.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31604917.
- Also identified by DOI 10.1038/s41467-019-12236-z and PMC identifier 6788984.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <sup>18</sup>F positron emission tomography (PET) DREADD radiotracer, [<sup>18</sup>F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [<sup>18</sup>F]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.
Medical subject headings
- Designer Drugs
- Fluorine Radioisotopes
- Neuronal Tract-Tracers