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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.
Affiliation
  • Bonaventura J; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Eldridge MAG; Laboratory of Neuropsychology, National Institute of Mental Health Intramural Research Program, Bethesda, MD, 20892, USA.
  • Hu F; Department of Radiology Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
  • Gomez JL; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Sanchez-Soto M; Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, MD, 20814, USA.
  • Abramyan AM; Computational Chemistry and Molecular Biophysics Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Lam S; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Boehm MA; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Ruiz C; Department of Neurobiology & Behavior, University of California, Irvine, CA, 92697, USA.
  • Farrell MR; Department of Neurobiology & Behavior, University of California, Irvine, CA, 92697, USA.
  • Moreno A; Department of Molecular Biology and Genetics, Dandrite, Aarhus University, 8000 Aarhus C, Aarhus, Denmark.
  • Galal Faress IM; Department of Molecular Biology and Genetics, Dandrite, Aarhus University, 8000 Aarhus C, Aarhus, Denmark.
  • Andersen N; Department of Molecular Biology and Genetics, Dandrite, Aarhus University, 8000 Aarhus C, Aarhus, Denmark.
  • Lin JY; School of Medicine, College of Health and Medicine, University of Tasmania, Tasmania, TAS, 7000, Australia.
  • Moaddel R; Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, Baltimore, MD, 21224, USA.
  • Morris PJ; National Center for Advancing Translational Sciences, Rockville, MD, 20850, USA.
  • Shi L; Computational Chemistry and Molecular Biophysics Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Sibley DR; Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, MD, 20814, USA.
  • Mahler SV; Department of Neurobiology & Behavior, University of California, Irvine, CA, 92697, USA.
  • Nabavi S; Department of Molecular Biology and Genetics, Dandrite, Aarhus University, 8000 Aarhus C, Aarhus, Denmark.
  • Pomper MG; Department of Radiology Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
  • Bonci A; Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
  • Horti AG; Department of Radiology Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. ahorti1@jhmi.edu.
  • Richmond BJ; Laboratory of Neuropsychology, National Institute of Mental Health Intramural Research Program, Bethesda, MD, 20892, USA. barryrichmond@mail.nih.gov.
  • Michaelides M; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA. mike.michaelides@nih.gov.
Nat Commun ; 10(1): 4627, 2019 10 11.
Article in En | MEDLINE | ID: mdl-31604917
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fluorine Radioisotopes / Designer Drugs / Neuronal Tract-Tracers Limits: Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fluorine Radioisotopes / Designer Drugs / Neuronal Tract-Tracers Limits: Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2019 Document type: Article Affiliation country: Country of publication: