Clozapine N-oxide

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Cat.No. 4936 - Clozapine N-oxide | C18H19ClN4O | CAS No. 34233-69-7
Description: Activator of muscarinic DREADDs
Chemical Name: 8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
Purity: ≥99% (HPLC)
Citations (31)
Reviews (7)

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
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
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.

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 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, 5HT2A/2C, non-selective, receptors, serotonin, 5HT2C, 5HT2, 5HT2A, dopaminergic, dopamine, antagonists, D4, clozapine-N-oxide, DREADDs, DREADD, Ligands, muscarnic, designer, CNO, Multidrug, Transporters, Non-selective, Muscarinics, 4936, Tocris Bioscience

31 Citations for Clozapine N-oxide

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

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

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

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

Nam et al (2019) Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference Cell Rep 28 1154 PMID: 31365861

McIver et al (2019) Maladaptive Downregulation of Autonomous Subthalamic Nucleus Activity following the Loss of Midbrain Dopamine Neurons Cell Rep 28 992 PMID: 31340159

Ma et al (2019) Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst. J Physiol

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

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

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

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

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

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

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

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

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

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

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 7 Reviews.)

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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

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