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High-potency ligands for DREADD imaging and activation in rodents and monkeys
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 an...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2019
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788984/ https://www.ncbi.nlm.nih.gov/pubmed/31604917 http://dx.doi.org/10.1038/s41467-019-12236-z |
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| author | Bonaventura, Jordi Eldridge, Mark A. G. Hu, Feng Gomez, Juan L. Sanchez-Soto, Marta Abramyan, Ara M. Lam, Sherry Boehm, Matthew A. Ruiz, Christina Farrell, Mitchell R. Moreno, Andrea Galal Faress, Islam Mustafa Andersen, Niels Lin, John Y. Moaddel, Ruin Morris, Patrick J. Shi, Lei Sibley, David R. Mahler, Stephen V. Nabavi, Sadegh Pomper, Martin G. Bonci, Antonello Horti, Andrew G. Richmond, Barry J. Michaelides, Michael |
| author_facet | Bonaventura, Jordi Eldridge, Mark A. G. Hu, Feng Gomez, Juan L. Sanchez-Soto, Marta Abramyan, Ara M. Lam, Sherry Boehm, Matthew A. Ruiz, Christina Farrell, Mitchell R. Moreno, Andrea Galal Faress, Islam Mustafa Andersen, Niels Lin, John Y. Moaddel, Ruin Morris, Patrick J. Shi, Lei Sibley, David R. Mahler, Stephen V. Nabavi, Sadegh Pomper, Martin G. Bonci, Antonello Horti, Andrew G. Richmond, Barry J. Michaelides, Michael |
| author_sort | Bonaventura, Jordi |
| collection | PubMed |
| description | 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 (18)F positron emission tomography (PET) DREADD radiotracer, [(18)F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [(18)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. |
| format | Online Article Text |
| id | pubmed-6788984 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-67889842019-10-15 High-potency ligands for DREADD imaging and activation in rodents and monkeys Bonaventura, Jordi Eldridge, Mark A. G. Hu, Feng Gomez, Juan L. Sanchez-Soto, Marta Abramyan, Ara M. Lam, Sherry Boehm, Matthew A. Ruiz, Christina Farrell, Mitchell R. Moreno, Andrea Galal Faress, Islam Mustafa Andersen, Niels Lin, John Y. Moaddel, Ruin Morris, Patrick J. Shi, Lei Sibley, David R. Mahler, Stephen V. Nabavi, Sadegh Pomper, Martin G. Bonci, Antonello Horti, Andrew G. Richmond, Barry J. Michaelides, Michael Nat Commun Article 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 (18)F positron emission tomography (PET) DREADD radiotracer, [(18)F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [(18)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. Nature Publishing Group UK 2019-10-11 /pmc/articles/PMC6788984/ /pubmed/31604917 http://dx.doi.org/10.1038/s41467-019-12236-z Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Bonaventura, Jordi Eldridge, Mark A. G. Hu, Feng Gomez, Juan L. Sanchez-Soto, Marta Abramyan, Ara M. Lam, Sherry Boehm, Matthew A. Ruiz, Christina Farrell, Mitchell R. Moreno, Andrea Galal Faress, Islam Mustafa Andersen, Niels Lin, John Y. Moaddel, Ruin Morris, Patrick J. Shi, Lei Sibley, David R. Mahler, Stephen V. Nabavi, Sadegh Pomper, Martin G. Bonci, Antonello Horti, Andrew G. Richmond, Barry J. Michaelides, Michael High-potency ligands for DREADD imaging and activation in rodents and monkeys |
| title | High-potency ligands for DREADD imaging and activation in rodents and monkeys |
| title_full | High-potency ligands for DREADD imaging and activation in rodents and monkeys |
| title_fullStr | High-potency ligands for DREADD imaging and activation in rodents and monkeys |
| title_full_unstemmed | High-potency ligands for DREADD imaging and activation in rodents and monkeys |
| title_short | High-potency ligands for DREADD imaging and activation in rodents and monkeys |
| title_sort | high-potency ligands for dreadd imaging and activation in rodents and monkeys |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788984/ https://www.ncbi.nlm.nih.gov/pubmed/31604917 http://dx.doi.org/10.1038/s41467-019-12236-z |
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