ArticlePloS one2020
Compound 21, a two-edged sword with both DREADD-selective and off-target outcomes in rats.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Changing subplate circuits: Early activity dependent circuit plasticity.Frontiers in cellular neuroscience · 2022Pooled it
- Off-target effects of DREADD ligands revealed by an anesthesia emergence paradigm in mice.Cell reports methods · 2026Article
- Facilitation of hippocampal long-term potentiation by astrocytic Gq signaling is compromised in an advanced Alzheimer's disease model.Scientific reports · 2026Article
- Advances in chemogenetics: a review of DREADDs and its application in psychiatric disorders.Molecular psychiatry · 2026Review
- Sex-dependent modulation of behavioral allocation via ventral tegmental area-nucleus accumbens shell circuitry.NeuroImmune pharmacology and therapeutics · 2025Article
- The role of electroencephalography in epilepsy research-From seizures to interictal activity and comorbidities.Epilepsia · 2025Review
- Neuromodulation in Small Animal fMRI.Journal of magnetic resonance imaging : JMRI · 2025Review
- Chemogenetic Tools and their Use in Studies of Neuropsychiatric Disorders.Physiological research · 2024Review
- Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools.Current opinion in neurobiology · 2024Review
- Clozapine N-oxide, compound 21, and JHU37160 do not influence effortful reward-seeking behavior in mice.Psychopharmacology · 2024Article
- DREADD agonist compound 21 causes acute diuresis in wild-type mice.Frontiers in pharmacology · 2024Article
- The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.Frontiers in neural circuits · 2024Article
- Acute In Vivo Administration of Compound 21 Stimulates Akt and ERK1/2 Phosphorylation in Mouse Heart and Adipose Tissue.International journal of molecular sciences · 2023Article
- Advanced neurobiological tools to interrogate metabolism.Nature reviews. Endocrinology · 2023Review
- Comparison of three DREADD agonists acting on Gq-DREADDs in the ventral tegmental area to alter locomotor activity in tyrosine hydroxylase:Cre male and female rats.Behavioural brain research · 2023Article
- A head-to-head comparison of two DREADD agonists for suppressing operant behavior in rats via VTA dopamine neuron inhibition.Psychopharmacology · 2023Article
- High dose administration of DREADD agonist JHU37160 produces increases in anxiety-like behavior in male rats.Behavioural brain research · 2023Article
- A head-to-head comparison of two DREADD agonists for suppressing operant behavior in rats via VTA dopamine neuron inhibition.bioRxiv : the preprint server for biology · 2023Article
- Article
- Medial and dorsal lateral septum involving social disruption stress-primed escalation in acid-induced writhes.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) represent a technical revolution in integrative neuroscience. However, the first used ligands exhibited dose-dependent selectivity for their molecular target, leading to potential unspecific effects. Compound 21 (C21) was recently proposed as an alternative, but in vivo characterization of its properties is not sufficient yet. Here, we evaluated its potency to selectively modulate the activity of nigral dopaminergic (DA) neurons through the canonical DREADD receptor hM4Di using TH-Cre rats. In males, 1 mg.kg-1 of C21 strongly increased nigral neurons activity in control animals, indicative of a significant off-target effect. Reducing the dose to 0.5 mg.kg-1 circumvented this unspecific effect, while activated the inhibitory DREADDs and selectively reduced nigral neurons firing. In females, 0.5 mg.kg-1 of C21 induced a transient and residual off-target effect that may mitigated the inhibitory DREADDs-mediated effect. This study raises up the necessity to test selectivity and efficacy of chosen ligands for each new experimental condition.
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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.