Clozapine N-oxide

Pricing Availability Delivery Time Qty
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)
Datasheet
Citations (13)
Reviews (7)
Literature

Biological Activity

Metabolite of clozapine. 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.

All Tocris products are intended for laboratory research use only.

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 solvent of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 2.92 mL 14.58 mL 29.17 mL
5 mM 0.58 mL 2.92 mL 5.83 mL
10 mM 0.29 mL 1.46 mL 2.92 mL
50 mM 0.06 mL 0.29 mL 0.58 mL

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Product Datasheets

Certificate of Analysis / Product Datasheet
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Safety Datasheet

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 clozapine. 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 clozapine. 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, Non-selective, Dopamine, 5-HT2A, Receptors, 5-HT2C, Glutamate, (Metabotropic), Group, III, II, Multidrug, Transporters, 4936, Tocris Bioscience

13 Citations for Clozapine N-oxide

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

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

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

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

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


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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