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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
Water soluble salt also available.
This product contains 1 molar equivalent of ethanol.
Technical Data for Clozapine N-oxide
|Storage||Store at RT|
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|
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|
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
52 Citations for Clozapine N-oxide
Citations are publications that use Tocris products. Selected citations for Clozapine N-oxide include:
Morelli et al (2021) Identification of a population of peripheral sensory neurons that regulates blood pressure. Cell Rep 35 PMID: 34077727
Bruzsik et al (2021) Somatostatin neurons of the bed nucleus of stria terminalis enhance associative fear memory consolidation in mice. J Neurosci 41 1982 PMID: 33468566
Maldonado et al (2021) Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons. Curr Biol 31 322 PMID: 33157028
Borodovitsyna et al (2020) Anatomically and functionally distinct locus coeruleus efferents mediate opposing effects on anxiety-like behavior Neurobiology of Stress 13 PMID: 33344735
Dorst et al (2020) Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner. Nat Commun 11 5113 PMID: 33037215
Pati et al (2020) Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior ELife 9 PMID: 32955432
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
Gizowski & Bourque et al (2020) Sodium regulates clock time and output via an excitatory GABAergic pathway. Nature
Delcourte et al (2020) Astroglia in lateral habenula is essential for antidepressant efficacy of light BioRXiv - not yet peer reviewed
Cregg et al (2020) Brainstem neurons that command mammalian locomotor asymmetries. Nat Neurosci 23 730 PMID: 32393896
Deffains et al (2020) In vivo electrophysiological validation of DREADD-based inhibition of pallidal neurons in the non-human primate. Eur J Neurosci 53 2192 PMID: 32306446
Taylor et al (2019) Chemogenetic Activation of Adrenocortical Gq Signaling Causes Hyperaldosteronism and Disrupts Functional Zonation. J Clin Invest 130 83 PMID: 31738186
D'Agostino et al (2016) Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. PLoS Biol 5 PMID: 26974347
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
Meira et al (2018) A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Nat.Commun. 9 4163 PMID: 30301899
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
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
Chai et al (2017) Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence. Neuron 95 531 PMID: 28712653
Weiner et al (2019) Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation. Nat Commun 10 2477 PMID: 31171770
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
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
Yuan and Grutzendler (2016) Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity. J Neurosci 36 632 PMID: 26758850
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
Terburg et al (2018) The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study. Cell 175 723 PMID: 30340041
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
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
Gelegen et al (2018) Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation. Curr Biol 28 580 PMID: 29398217
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
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
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.)
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Soluble in 0.9% saline. Perfused in brain slice experiment with patch clamp study.
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.
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.
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
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.
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.
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.