ArticleACS chemical neuroscience2015
The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs.
Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
What it found
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Who cites it
98 citing papers in PubMed, 152 citations in OpenAlex.
- 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 · 2026Review
- Off-target effects of DREADD ligands revealed by an anesthesia emergence paradigm in mice.Cell reports methods · 2026Article
- Binding affinities for histamine receptors 1 to 4: Systematic comparison of ligands from the Psychoactive Drug Screening Program KMolecular pharmacology · 2026Review
- Facilitation of hippocampal long-term potentiation by astrocytic Gq signaling is compromised in an advanced Alzheimer's disease model.Scientific reports · 2026Article
- Selective reduction of KCNA4 in vulnerable glutamatergic-serotonin neurons of the dorsal raphe nucleus in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Pathway-specific regulation of the paraventricular thalamic nucleus in depressive-like behavior.Scientific reports · 2026Article
- Interrogating Physiological Functions with Light and Chemicals.Annual review of physiology · 2026Review
- DREADD agonist Clozapine-N-oxide, but not Compound 21, impairs spatial memory encoding.bioRxiv : the preprint server for biology · 2026Article
- Advances in chemogenetics: a review of DREADDs and its application in psychiatric disorders.Molecular psychiatry · 2026Review
- Clozapine-N-oxide impairs spatial memory independent of DREADDs.Frontiers in cellular neuroscience · 2026Article
- Reflex regulation of respiration and heart rate by inhaled activators of vagal bronchopulmonary afferents.Journal of neurophysiology · 2025Article
- Sex-dependent modulation of behavioral allocation via ventral tegmental area-nucleus accumbens shell circuitry.NeuroImmune pharmacology and therapeutics · 2025Article
- A top-down insular cortex circuit crucial for non-nociceptive fear learning.Science advances · 2025Article
- Article
- Review
- Methodology for Studying Hypothalamic Regulation of Feeding Behaviors.Methods and protocols · 2024Review
- Size-reduced DREADD derivatives for AAV-assisted multimodal chemogenetic control of neuronal activity and behavior.Cell reports methods · 2024Article
- Chemogenetic Tools and their Use in Studies of Neuropsychiatric Disorders.Physiological research · 2024Review
- Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance.Immunity · 2024Article
- Updated Toolbox for Assessing Neuronal Network Reconstruction after Cell Therapy.Bioengineering (Basel, Switzerland) · 2024Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand-receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure-activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3.
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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.