135335 - High potency ligands for DREADD.pdf (2.09 MB)
High-potency ligands for DREADD imaging and activation in rodents and monkeys
journal contribution
posted on 2023-05-20, 07:41 authored by Bonaventura, J, Eldridge, MAG, Hu, F, Gomez, JL, Sanchez-Soto, M, Abramyan, AM, Lam, S, Boehm, MA, Ruiz, C, Farrell, MR, Moreno, A, Faress, IMG, Andersen, N, John LinJohn Lin, Moaddel, R, Morris, PJ, Shi, L, Sibley, DR, Mahler, SV, Nabavi, S, Pomper, MG, Bonci, A, Horti, AG, Richmond, BJ, Michaelides, MDesigner 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
Funding
Lundbeck Foundation
History
Publication title
Nature communicationsVolume
10Article number
4627Number
4627Pagination
1-12ISSN
2041-1723Department/School
Tasmanian School of MedicinePublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2019 The Author(s) Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open