Evidence map›Paper›PMID 32632286›Full record

ArticleNature neuroscience2020

Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys.

Yuji Nagai, Naohisa Miyakawa, Hiroyuki Takuwa, Yukiko Hori, Kei Oyama, Bin Ji, Manami Takahashi, Xi-Ping Huang, Samuel T Slocum, Jeffrey F DiBerto and 21 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Nature neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06027190 (To Investigate the Clinical Efficacy of Optical 3D Navigation Repetitive Transcranial Magnetic Stimulation), which is not on this map. Cited by 257 papers.

0numbers the graph read from it
0cells of the map it votes in
257citing papers in PubMed
15.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06027190 nanot yet recruitingnot on this mapstarted 2024, after this paper: background citation

To Investigate the Clinical Efficacy of Optical 3D Navigation Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Achalasia, Optimize the Treatment Parameters, and Provide a Noninvasive Treatment Strategy for Achalasia

TypeinterventionalSponsorZhang NinaRan2024 to 2026Enrolled112ConditionsEsophageal Achalasia, Transcranial Magnetic Stimulation, Repetitive, Vagus Nerve Motor Disorder, Functional Magnetic Resonance ImagingArmsRepetitive transcranial magnetic stimulation, Sham
3 · Its place in the literature

Who cites it

257 citing papers in PubMed, 410 citations in OpenAlex.

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  7. Calbindin stratifies midbrain dopaminergic neurons governing distinct aspects of locomotion.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  8. Activation of GScience advances · 2026
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  9. Article
  10. Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  11. Article
  12. Regulation of the decision threshold by the locus coeruleus.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  13. Altered GScience advances · 2026
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197 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 5 institutions in 2 countries.

Yuji Nagai *Department of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.ORCID http://orcid.org/0000-0001-7005-0749
Naohisa Miyakawa *Department of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.ORCID http://orcid.org/0000-0001-5057-0333
Hiroyuki TakuwaDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Yukiko HoriDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Kei OyamaDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Bin JiDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Manami TakahashiDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Xi-Ping HuangDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Samuel T SlocumDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-5942-4367
Jeffrey F DiBertoDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Yan XiongMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Takuya UrushihataDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Toshiyuki HirabayashiDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Atsushi FujimotoDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.ORCID http://orcid.org/0000-0002-1621-2003
Koki MimuraDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Justin G EnglishDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-1161-8928
Jing LiuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ken-Ichi InoueSystems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Japan.ORCID http://orcid.org/0000-0002-5683-5280
Katsushi KumataDepartment of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Chie SekiDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Maiko OnoDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Masafumi ShimojoDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Ming-Rong ZhangDepartment of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Yutaka TomitaDepartment of Neurology, Keio University School of Medicine, Tokyo, Japan.
Jin NakaharaDepartment of Neurology, Keio University School of Medicine, Tokyo, Japan.
Tetsuya SuharaDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Masahiko TakadaSystems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Japan.
Makoto HiguchiDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-2387-3862
Bryan L RothDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA. bryan_roth@med.unc.edu.ORCID http://orcid.org/0000-0002-0561-6520
Takafumi MinamimotoDepartment of Functional Brain Imaging, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. minamimoto.takafumi@qst.go.jp.ORCID http://orcid.org/0000-0003-4305-0174
National Institutes for Quantum Science and Technology · JPUniversity of North Carolina at Chapel Hill · USIcahn School of Medicine at Mount Sinai · USKeio University · JPKyoto University · JP

Funding

Illuminating the Druggable GPCR-omeU24DK116195 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L., SHOICHET, BRIAN K · 2017 to 2022
$14.3M
DREADD2.0: AN ENHANCED CHEMOGENETIC TOOLKITU01MH105892 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JIN, JIAN, KASH, THOMAS L. · 2014 to 2016
$3.0M
NIDDK NIH HHS U24 DK116195NIMH NIH HHS U01 MH105892
6 · The paper itself

Abstract

The chemogenetic technology designer receptors exclusively activated by designer drugs (DREADDs) afford remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities and potential off-target effects of CNO represent areas for improvement. Here, we provide a new high-affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg per kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg per kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents a potent, selective, metabolically stable and fast-acting DREADD agonist with utility in both mice and nonhuman primates for a variety of applications.

Indexed as

AnimalsBehavior, AnimalBrainClozapineDesigner DrugsGenetic TechniquesHumansMacaca fuscataMacaca mulattaMiceMice, Inbred C57BLMice, TransgenicModels, AnimalNeuronsReceptor, Muscarinic M3Receptor, Muscarinic M411-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepineClozapineDesigner DrugsReceptor, Muscarinic M3Receptor, Muscarinic M4

Identifiers

PMID32632286
OpenAlexW3038591947

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.