Clozapine N-oxide

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Cat.No. 4936 - Clozapine N-oxide | C18H19ClN4O | CAS No. 34233-69-7
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)
Datasheet
Citations (50)
Reviews (8)
Literature (4)

Biological Activity

Metabolite of clozapine (Cat. No. 0444). Activates human muscarinic designer receptors (DREADDs) in vitro. Silences hippocampal neurons expressing hM4 DREADDs in vitro. Activates Gs-linked DREADDS- AgRP in mice via intracerebroventricular (i.c.v) injection. Shown to be a P-glycoprotein (P-gp) efflux pump substrate. Other potent and selective hM3Dq DREADD agonists available: DREADD agonist 21 and Perlapine.

Water soluble salt also available.

This product contains 1 molar equivalent of ethanol.

Technical Data

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

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 6.86 20

Preparing Stock Solutions

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.

Select a batch to recalculate based on the batch molecular weight:
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

Certificate of Analysis / Product Datasheet
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References

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.

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

50 Citations for Clozapine N-oxide

Citations are publications that use Tocris products. Selected citations for Clozapine N-oxide include:

Morelli et al (2020) Identification of a novel population of peripheral sensory neuron that regulates blood pressure BioRXiv - not yet peer reviewed

Deffains et al (2020) In vivo electrophysiological validation of DREADD-based inhibition of pallidal neurons in the non-human primate. Eur J Neurosci PMID: 32306446

Cregg et al (2020) Brainstem neurons that command mammalian locomotor asymmetries. Nat Neurosci 23 730 PMID: 32393896

Delcourte et al (2020) Astroglia in lateral habenula is essential for antidepressant efficacy of light BioRXiv - not yet peer reviewed

Pati et al (2020) Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior ELife 9 PMID: 32955432

Dorst et al (2020) Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner. Nat Commun 11

Bruzsik et al (2020) Somatostatin neurons of the bed nucleus of stria terminalis enhance associative fear memory consolidation in mice. BioRXiv - not yet peer reviewed

Gizowski & Bourque et al (2020) Sodium regulates clock time and output via an excitatory GABAergic pathway. Nature

Hart et al (2020) Chemogenetic Modulation and Single-Photon Calcium Imaging in Anterior Cingulate Cortex Reveal a Mechanism for Effort-Based Decisions J Neurosci 40 5628 PMID: 32527984

Aggarwal et al (2018) Medial Amygdala Kiss1 Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice. Neuroendocrinology 108 172 PMID: 30537700

Leroy et al (2018) A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature 564 213 PMID: 30518859

Glasgow et al (2018) Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus. Cell Rep 25 168 PMID: 30282026

Pina and Cunningham (2016) Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit. Neurobiol Learn Mem 137 83 PMID: 27866960

D'Agostino et al (2016) Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. PLoS Biol 5 PMID: 26974347

Weiner et al (2019) Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation. Nat Commun 10 2477 PMID: 31171770

Adamsky et al (2018) Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. Cell 174 59 PMID: 29804835

Cembrowski et al (2018) Dissociable Structural and Functional Hippocampal Outputs via Distinct Subiculum Cell Classes. Cell 173 1280 PMID: 29681453

Alhadeff et al (2018) A Neural Circuit for the Suppression of Pain by a Competing Need State. Cell 173 140 PMID: 29570993

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

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

Yuan and Grutzendler (2016) Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity. J Neurosci 36 632 PMID: 26758850

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

Amat (2017) Using c-kit to genetically target cerebellar molecular layer interneurons in adult mice. PLoS One 12 e0179347 PMID: 28658323

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

Taylor et al (2019) Chemogenetic Activation of Adrenocortical Gq Signaling Causes Hyperaldosteronism and Disrupts Functional Zonation. J Clin Invest 130 83 PMID: 31738186

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

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

Attinger (2017) Visuomotor coupling shapes the functional development of mouse visual cortex. Cell 169 1291 PMID: 28602353

Berglind et al (2018) Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures. Sci Rep 8 5669 PMID: 29618778

Hardy et al (2018) The role of calretinin-expressing granule cells in olfactory bulb functions and odor behavior. Sci Rep 8 9385 PMID: 29925844

Terburg et al (2018) The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study. Cell 175 723 PMID: 30340041

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

Heiss et al (2018) Parallel Arousal Pathways in the Lateral Hypothalamus. Eneuro 5 PMID: 30225361

Chai et al (2017) Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence. Neuron 95 531 PMID: 28712653

Francois et al (2017) A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins. Neuron 93 822 PMID: 28162807

Heinsbroek et al (2017) Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking. J Neurosci 37 757 PMID: 28123013

Meira et al (2018) A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Nat.Commun. 9 4163 PMID: 30301899

Tan et al (2016) Warm-Sensitive Neurons that Control Body Temperature. Cell 167 47 PMID: 27616062

Lim et al (2016) Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci 19 1073 PMID: 27399843

Smith et al (2016) DREADDS: Use and application in behavioral neuroscience. Behav Neurosci 130 137 PMID: 26913540


Do you know of a great paper that uses Clozapine N-oxide from Tocris? Please let us know.

Reviews for Clozapine N-oxide

Average Rating: 4.6 (Based on 8 Reviews.)

5 Star
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Good product.
By Anonymous on 06/15/2020
Assay Type: In Vivo
Species: Mouse
Cell Line/Tissue: neuron

1 mg/kg

PMID: 31340159 Reference
review image

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.

review image

CNO in DREADD pain targeted Mice.
By Anonymous on 12/15/2017
Species: Mouse

CNO was used in pair with DREADD mice for a pain related experiment to determine whether inhibiting PBN neurons will attenuate pain reponses. Publication under second revision for Cell.

Product provides publishable work, no issues arose when dealing with the substance.


CNO in concert with DREADDs.
By Anonymous on 12/01/2017
Species: Rat

I injected clozapine N-oxide in rats (IP, 1 mg/ml/kg). The rats had previously underwent stereotaxic surgery in which a virus carrying a gene for a Gi DREADD was infused unilaterally into the dorsal striatum.


CNO for chronic DREADD activation.
By Anonymous on 12/01/2017
Assay Type: In Vivo
Species: Mouse

In vivo chemogenetic experiments - CNO was added to the drinking water. While there are issues with the back conversion of CNO to clozapine, this is not the manufacturer's problem. CNO experiments still generate important data as long as they utilize proper controls

Added saccharine to counteract bitter taste of DMSO used to dissolve CNO


Does what it is meant to!.
By Anonymous on 10/20/2017
Assay Type: In Vivo
Species: Rat

We use it as both injectable pass the blood brain barrier ICV, and IP injections. We are looking at both behavioral concern and brain regional efficacy in regard to DREADD. So far, this product has been selectively turning on/off our target cells.


tail bleed.
By Anonymous on 09/07/2017
Assay Type: Ex Vivo
Species: Mouse

bleed assay


neuron silencer.
By Anonymous on 07/17/2017
Assay Type: In Vivo
Species: Mouse

neuron silencer


Literature in this Area

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