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Submit ReviewClozapine N-oxide
Description: Activator of hM3Dq and hM4Di DREADDs
Alternative Names: CNO
Chemical Name: 8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
Purity: ≥99% (HPLC)
Biological Activity for Clozapine N-oxide
Clozapine N-oxide is a synthetic ligand for human muscarinic engineered receptors, designer receptors activated by designer drugs (DREADD). Binds and activates hM3Dq and hM4Di DREADDs in vitro and in vivo. Metabolite of Clozapine (Cat. No. 0444). Shown to be a P-glycoprotein (P-gp) efflux pump substrate.
Example Applications of Clozapine N-oxide (CNO):
- Silences hippocampal neurons expressing hM4Di DREADDs in vitro
- Inhibits locomotor activity of mice expressing hM3Dq in GABAergic VTA neurons
- Inhibits short term memory retrieval in mice expressing hM4Di in hippocampal neurons
- Induces heat and mechanical hypersensitivity in mice expressing hM4Di in enkephalinergic neurons in the right lumbar dorsal horn
- Inhibits markers of social aggression in mice expressing hM4Di in hippocampal CA2 neurons
Alternative potent and selective hM3Dq and hM4Di DREADD agonists available: Deschloroclozapine and DREADD agonist 21
Water soluble salt also available.
This product contains 1 molar equivalent of ethanol.
Technical Data for Clozapine N-oxide
| M. Wt | 342.82 |
| Formula | C18H19ClN4O |
| Storage | Store at RT |
| Purity | ≥99% (HPLC) |
| CAS Number | 34233-69-7 |
| PubChem ID | 2819 |
| InChI Key | WYRDWWAASBTJLM-UHFFFAOYSA-N |
| Smiles | ClC(C=C3)=CC1=C3NC(C=CC=C2)=C2C(N4CC[N+](C)([O-])CC4)=N1 |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Solubility Data for Clozapine N-oxide
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 6.86 | 20 |
Preparing Stock Solutions for Clozapine N-oxide
The following data is based on the product molecular weight 342.82. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 0.2 mM | 14.58 mL | 72.92 mL | 145.85 mL |
| 1 mM | 2.92 mL | 14.58 mL | 29.17 mL |
| 2 mM | 1.46 mL | 7.29 mL | 14.58 mL |
| 10 mM | 0.29 mL | 1.46 mL | 2.92 mL |
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Product Datasheets for Clozapine N-oxide
References for Clozapine N-oxide
References are publications that support the biological activity of the product.
Eiermann et al (1997) The involvement of CYP1A2 and CYP3A4 in the metabolism of cloz. Br.J.Clin.Pharmacol. 44 439 PMID: 9384460
Armbruster et al (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc.Natl.Acad.Sci.U.S.A. 104 5163 PMID: 17360345
Zaman et al (2014) LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia. J.Neurosci. 34 140 PMID: 24381275
Gomez et al (2017) Chemogenetics revealed: DREADD occupancy and activation via converted cloz. Science 357 503 PMID: 28774929
Nakajima et al (2016) Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat.Commun. 8 10268 PMID: 26743492
Roth (2016) DREADDs for Neuroscientists. Neuron 89 683 PMID: 26889809
If you know of a relevant reference for Clozapine N-oxide, please let us know.
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Keywords: Clozapine N-oxide, Clozapine N-oxide supplier, clozapine, metabolite, clozapine-N-oxide, DREADDs, DREADD, Ligands, muscarnic, receptors, designer, CNO, chemogenetics, Multidrug, Transporters, Non-selective, Muscarinics, 4936, Tocris Bioscience
139 Citations for Clozapine N-oxide
Citations are publications that use Tocris products. Selected citations for Clozapine N-oxide include:
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Gelegen et al (2018) Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation. Curr Biol 28 580 PMID: 29398217
Harding et al (2018) A Neuronal Hub Binding Sleep Initiation and Body Cooling in Response to a Warm External Stimulus. Curr Biol 28 2263 PMID: 30017485
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Lu et al (2019) Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons. Nat.commun. 10 1029 PMID: 30833673
Jarovi et al (2019) Prefrontal Theta Oscillations Promote Selective Encoding of Behaviorally Relevant Events. Eneuro 5 PMID: 30693310
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Hardy et al (2018) The role of calretinin-expressing granule cells in olfactory bulb functions and odor behavior. Sci Rep 8 9385 PMID: 29925844
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Rapanelli (2017) Histamine modulation of the basal ganglia circuitry in the development of pathological grooming. Proc Natl Acad Sci U S A. 114 6599 PMID: 28584117
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Qiao et al (2021) PDX1LOW MAFALOW β-cells contribute to islet function and insulin release. Nat Commun 12 674 PMID: 33514698
Alfred J et al (2021) An excitatory lateral hypothalamic circuit orchestrating pain behaviors in mice. Elife 10 PMID: 34042586
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Jason et al (2021) Loss of nigral excitation of cholinergic interneurons contributes to parkinsonian motor impairments. Neuron 109 1137-1149.e5 PMID: 33600762
Xiaolin et al (2021) Enhancing mask activity in dopaminergic neurons extends lifespan in flies. Aging Cell 20 e13493 PMID: 34626525
Alan C et al (2021) ARCGHR Neurons Regulate Muscle Glucose Uptake. Cells 10 PMID: 34063647
Richard et al (2021) Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats. Elife 10 PMID: 33555256
Carlos et al (2021) A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories. Elife 10 PMID: 34142660
David P et al (2021) NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity. Nat Commun 12 5175 PMID: 34462445
Sarah et al (2021) Lateral hypothalamic LEPR neurons drive appetitive but not consummatory behaviors. Cell Rep 36 109615 PMID: 34433027
Yavin et al (2021) A neural substrate of compulsive alcohol use. Sci Adv 7 PMID: 34407947
Luis et al (2021) Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice. J Clin Invest 131 PMID: 33848272
Wei et al (2021) Presymptomatic training mitigates functional deficits in a mouse model of Rett syndrome. Nature 592 596-600 PMID: 33762729
Jonathan N et al (2021) tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice. Elife 10 PMID: 33704065
Máté et al (2021) Neurochemically distinct populations of the bed nucleus of stria terminalis modulate innate fear response to weak threat evoked by predator odor stimuli. Neurobiol Stress 15 100415 PMID: 34765699
Peter et al (2021) Locomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neurons. Nat Commun 12 3251 PMID: 34059686
Jae-Hong et al (2021) Chemogenetic stimulation of the Gi pathway in astrocytes suppresses neuroinflammation. Pharmacol Res Perspect 9 e00822 PMID: 34676988
Naoya et al (2021) Thalamic input to motor cortex facilitates goal-directed action initiation. Curr Biol 31 4148-4155.e4 PMID: 34302741
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Sarah A et al (2021) Top-down control of conditioned overconsumption is mediated by insular cortex Nos1 neurons. Cell Metab 33 1418-1432.e6 PMID: 33761312
Giovanni et al (2021) Specific and behaviorally consequential astrocyte Gq GPCR signaling attenuation in vivo with iβARK. Neuron 109 2256-2274.e9 PMID: 34139149
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Sarah et al (2021) Hypothalamic control of interoceptive hunger. Curr Biol 31 3797-3809.e5 PMID: 34273280
Chris et al (2021) Chronic chemogenetic stimulation of the anterior olfactory nucleus reduces newborn neuron survival in the adult mouse olfactory bulb. J Neurochem 158 1186-1198 PMID: 34338310
Lei et al (2021) Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval. Neurosci Bull 37 229-241 PMID: 33180308
Chiara et al (2021) A functional map for diverse forelimb actions within brainstem circuitry. Nature 590 445-450 PMID: 33408409
Weiner et al (2019) Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation. Nat Commun 10 2477 PMID: 31171770
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McIver et al (2019) Maladaptive Downregulation of Autonomous Subthalamic Nucleus Activity following the Loss of Midbrain Dopamine Neurons Cell Rep 28 992 PMID: 31340159
Nam et al (2019) Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference Cell Rep 28 1154 PMID: 31365861
Ma et al (2019) Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst. J Physiol 597 4851 PMID: 31390064
Ma et al (2019) Galanin Neurons Unite Sleep Homeostasis and α2-Adrenergic Sedation Curr Biol 29 3315 PMID: 31543455
Nasrallah et al (2019) Routing Hippocampal Information Flow through Parvalbumin Interneuron Plasticity in Area CA2. Cell Rep 27 86 PMID: 30943417
Cornelia et al (2017) Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice. Proc Natl Acad Sci U S A 114 4525-4530 PMID: 28396414
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Martin et al (2017) CaMKIIα Expression Defines Two Functionally Distinct Populations of Granule Cells Involved in Different Types of Odor Behavior. Curr Biol 27 3315-3329.e6 PMID: 29107547
Zhang et al (2017) Inhibiting medial septal cholinergic neurons with DREADD alleviated anxiety-like behaviors in mice. Neurosci Letts 18 139 PMID: 27939976
Roman et al (2017) A tale of two circuits: CCKNTS neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions. Neuroscience 358 316 PMID: 28684275
Pina and Cunningham et al (2017) Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit. Neurobiol Learn Mem 137 83 PMID: 27866960
Ge et al (2017) Glutamatergic projections from the entorhinal cortex to dorsal dentate gyrus mediate context-induced reinstatement of heroin seeking. Neuropsychopharmacology 42 1860 PMID: 28106041
Schwartz et al (2017) Cortico-accumbens regulation of approach-avoidance behavior Is modified by experience and chronic pain. Cell Rep 19 1522 PMID: 28538173
Amat (2017) Using c-kit to genetically target cerebellar molecular layer interneurons in adult mice. PLoS One 12 e0179347 PMID: 28658323
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Danny G et al (2022) High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice. Mol Metab 64 101571 PMID: 35953023
Dora et al (2022) Median raphe region GABAergic neurons contribute to social interest in mouse. Life Sci 289 120223 PMID: 34896160
Rubén et al (2022) Hypothalamic pregnenolone mediates recognition memory in the context of metabolic disorders. Cell Metab 34 269-284.e9 PMID: 35108514
Tsung-Chih et al (2022) Distinct Contribution of Granular and Agranular Subdivisions of the Retrosplenial Cortex to Remote Contextual Fear Memory Retrieval. J Neurosci 42 877-893 PMID: 34876468
Shun-Fen et al (2022) High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens. Mol Psychiatry 27 4372-4384 PMID: 36180573
Simon M et al (2022) Hypothalamic AgRP neurons exert top-down control on systemic TNF-α release during endotoxemia. Curr Biol 32 4699-4706.e4 PMID: 36182699
Erik et al (2022) TRAPing Ghrelin-Activated Circuits: A Novel Tool to Identify, Target and Control Hormone-Responsive Populations in TRAP2 Mice. Int J Mol Sci 23 PMID: 35008985
Carsten T et al (2022) Why do mice squeak? Toward a better understanding of defensive vocalization. iScience 25 104657 PMID: 35845167
George Z et al (2022) Control of mammalian locomotion by ventral spinocerebellar tract neurons. Cell 185 328-344.e26 PMID: 35063074
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Domokos et al (2022) Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions. J Exp Med 219 PMID: 35201268
Tian et al (2022) Auts2 deletion involves in DG hypoplasia and social recognition deficit: The developmental and neural circuit mechanisms. Sci Adv 8 eabk1238 PMID: 35235353
Jing et al (2022) Parvalbumin Neurons in Zona Incerta Regulate Itch in Mice. Front Mol Neurosci 15 843754 PMID: 35299695
Sonia et al (2022) Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1. Cell Rep 39 110667 PMID: 35417707
J Silvio et al (2019) Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. J Biol Chem 294 531-546 PMID: 30446620
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Giovanni et al (2019) Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue. Cell 177 1280-1292.e20 PMID: 31031006
Shinae et al (2019) Distinct roles of striatal direct and indirect pathways in value-based decision making. Elife 8 PMID: 31310237
Laura et al (2019) Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice. Curr Biol 29 1938-1953.e6 PMID: 31178317
Jeffrey S et al (2019) Recruitment of Spinoparabrachial Neurons by Dorsal Horn Calretinin Neurons. Cell Rep 28 1429-1438.e4 PMID: 31390558
J Nicholas et al (2019) Natural and Drug Rewards Engage Distinct Pathways that Converge on Coordinated Hypothalamic and Reward Circuits. Neuron 103 891-908.e6 PMID: 31277924
J Silvio et al (2019) Illuminating G-Protein-Coupling Selectivity of GPCRs. Cell 177 1933-1947.e25 PMID: 31160049
Adekunbi et al (2018) Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice. J Neuroendocrinol 30 e12572 PMID: 29356147
Jiang et al (2018) Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain. Neurosci Letts 671 7 PMID: 29410218
Christopher J et al (2018) Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior. Neuron 99 1170-1187.e9 PMID: 30174118
Jasper et al (2020) Value-guided remapping of sensory cortex by lateral orbitofrontal cortex. Nature 585 245-250 PMID: 32884146
Giovanni et al (2020) Context-Specific Striatal Astrocyte Molecular Responses Are Phenotypically Exploitable. Neuron 108 1146-1162.e10 PMID: 33086039
Stewart A et al (2020) Modular, Circuit-Based Interventions Rescue Hippocampal-Dependent Social and Spatial Memory in a 22q11.2 Deletion Syndrome Mouse Model. Biol Psychiatry 88 710-718 PMID: 32682567
John Q et al (2020) Neuronal activity modulates alpha-synuclein aggregation and spreading in organotypic brain slice cultures and in vivo. Acta Neuropathol 140 831-849 PMID: 33021680
Peng et al (2020) Brain Circuit of Claustrophobia-like Behavior in Mice Identified by Upstream Tracing of Sighing. Cell Rep 31 107779 PMID: 32553161
J Silvio et al (2020) Activation of G-Protein Coupled Receptor-Gαi Signaling Increases Keratinocyte Proliferation and Reduces Differentiation, Leading to Epidermal Hyperplasia. J Invest Dermatol 140 1195-1203.e3 PMID: 31707029
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J Silvio et al (2020) Gαs directly drives PDZ-RhoGEF signaling to Cdc42. J Biol Chem 295 16920-16928 PMID: 33023908
Masahiro et al (2020) Developmental Phase Transitions in Spatial Organization of Spontaneous Activity in Postnatal Barrel Cortex Layer 4. J Neurosci 40 7637-7650 PMID: 32887743
Wei-Yang et al (2020) Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice. Brain Behav Immun 88 791-801 PMID: 32434046
Filippo et al (2020) Specific Hippocampal Interneurons Shape Consolidation of Recognition Memory. Cell Rep 32 108046 PMID: 32814049
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Mark S et al (2020) A Sparse, Spatially Biased Subtype of Mature Granule Cell Dominates Recruitment in Hippocampal-Associated Behaviors. Cell Rep 31 107551 PMID: 32348756
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By
Anonymous on 06/15/2020
Assay Type: In Vivo
Species: Mouse
Cell Line/Tissue: neuron
1 mg/kg
Highly soluble and stable.
By
Anonymous on 01/04/2018
Assay Type: Ex Vivo
Species: Mouse
Soluble in 0.9% saline. Perfused in brain slice experiment with patch clamp study.
Literature in this Area
Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Chemogenetics Research Bulletin
Produced by Tocris, the chemogenetics research bulletin provides an introduction to chemogenetic methods to manipulate neuronal activity. It outlines the development of RASSLs, DREADDs and PSAMs, and the use of chemogenetic compounds. DREADD ligands and PSEMs available from Tocris are highlighted.
Allosteric GPCR Pharmacology Poster
G protein-coupled receptors (GPCRs) are intrinsically allosteric proteins. This poster provides insights into allosteric mechanisms of GPCR biology, highlighting key facets of GPCR allostery and therapeutic applications of allosteric modulators.
GPCR Efficacy and Biased Agonism Poster
GPCRs can interact with multiple distinct transducers or regulatory proteins and these can be preferentially engaged in an agonist-specific manner giving rise to biased agonism. This poster discusses cutting edge GPCR signaling pharmacology and highlights therapeutic applications of biased agonism.