Clozapine N-oxide
Chemical Name: 8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
Purity: ≥99%
Biological Activity
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
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.
Background References
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Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.
Nakajima et al.
Nat. Commun., 2016;8:10268 -
Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.
Ambruster et al.
Proc.Natl.Acad.Sci.U.S.A., 2007;104:5163 -
LMO4 is essential for paraventricular hypothalamic neuronal activity and calcium channel expression to prevent hyperphagia.
Zaman et al.
J.Neurosci., 2014;34:140 -
DREADDs for Neuroscientists.
Roth et al.
Neuron, 2016;89:683 -
The involvement of CYP1A2 and CYP3A4 in the metabolism of cloz.
Eiermann et al.
Br.J.Clin.Pharmacol., 1997;44:439 -
Chemogenetics revealed: DREADD occupancy and activation via converted cloz.
Gomez et al.
Science, 2017;357:503
Product Datasheets
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Citations for Clozapine N-oxide
The citations listed below are publications that use Tocris products. Selected citations for Clozapine N-oxide include:
53 Citations: Showing 1 - 10
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Transient Receptor Potential Ankyrin-1-expressing vagus nerve fibers mediate IL-1� induced hypothermia and reflex anti-inflammatory responses
Authors: Silverman Et al.
Mol Med 2023;29:4
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Somatostatin neurons of the bed nucleus of stria terminalis enhance associative fear memory consolidation in mice.
Authors: Bruzsik Et al.
J Neurosci 2021;41:1982
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Identification of a population of peripheral sensory neurons that regulates blood pressure.
Authors: Morelli Et al.
Cell Rep 2021;35
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Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons.
Authors: Maldonado Et al.
Curr Biol 2021;31:322
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Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior
Authors: Pati Et al.
ELife 2020;9
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In vivo electrophysiological validation of DREADD-based inhibition of pallidal neurons in the non-human primate.
Authors: Deffains Et al.
Eur J Neurosci 2020;53:2192
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Chemogenetic Modulation and Single-Photon Calcium Imaging in Anterior Cingulate Cortex Reveal a Mechanism for Effort-Based Decisions
Authors: Hart Et al.
J Neurosci 2020;40:5628
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Brainstem neurons that command mammalian locomotor asymmetries.
Authors: Cregg Et al.
Nat Neurosci 2020;23:730
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Anatomically and functionally distinct locus coeruleus efferents mediate opposing effects on anxiety-like behavior
Authors: Borodovitsyna Et al.
Neurobiology of Stress 2020;13
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Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner.
Authors: Dorst Et al.
Nat Commun 2020;11:5113
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Astroglia in lateral habenula is essential for antidepressant efficacy of light
Authors: Delcourte Et al.
BioRXiv - not yet peer reviewed 2020;
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Sodium regulates clock time and output via an excitatory GABAergic pathway.
Authors: Gizowski & Bourque Et al.
Nature 2020;
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Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst.
Authors: Ma Et al.
J Physiol 2019;597:4851
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Prefrontal Theta Oscillations Promote Selective Encoding of Behaviorally Relevant Events.
Authors: Jarovi Et al.
Eneuro 2019;5
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Galanin Neurons Unite Sleep Homeostasis and α2-Adrenergic Sedation
Authors: Ma Et al.
Curr Biol 2019;29:3315
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Maladaptive Downregulation of Autonomous Subthalamic Nucleus Activity following the Loss of Midbrain Dopamine Neurons
Authors: McIver Et al.
Cell Rep 2019;28:992
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Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference
Authors: Nam Et al.
Cell Rep 2019;28:1154
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Routing Hippocampal Information Flow through Parvalbumin Interneuron Plasticity in Area CA2.
Authors: Nasrallah Et al.
Cell Rep 2019;27:86
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Chemogenetic Activation of Adrenocortical Gq Signaling Causes Hyperaldosteronism and Disrupts Functional Zonation.
Authors: Taylor Et al.
J Clin Invest 2019;130:83
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Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.
Authors: Weiner Et al.
Nat Commun 2019;10:2477
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Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons.
Authors: Lu Et al.
Nat.commun. 2019;10:1029
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A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics.
Authors: Meira Et al.
Nat.Commun. 2018;9:4163
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The role of calretinin-expressing granule cells in olfactory bulb functions and odor behavior.
Authors: Hardy Et al.
Sci Rep 2018;8:9385
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Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures.
Authors: Berglind Et al.
Sci Rep 2018;8:5669
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Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain.
Authors: Jiang Et al.
Neurosci Letts 2018;671:7
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A circuit from hippocampal CA2 to lateral septum disinhibits social aggression.
Authors: Leroy Et al.
Nature 2018;564:213
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Parallel Arousal Pathways in the Lateral Hypothalamus.
Authors: Heiss Et al.
Eneuro 2018;5
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Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.
Authors: Adekunbi Et al.
J Neuroendocrinol 2018;30:e12572
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Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation.
Authors: Gelegen Et al.
Curr Biol 2018;28:580
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A Neuronal Hub Binding Sleep Initiation and Body Cooling in Response to a Warm External Stimulus.
Authors: Harding Et al.
Curr Biol 2018;28:2263
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Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus.
Authors: Glasgow Et al.
Cell Rep 2018;25:168
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The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study.
Authors: Terburg Et al.
Cell 2018;175:723
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Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement.
Authors: Adamsky Et al.
Cell 2018;174:59
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A Neural Circuit for the Suppression of Pain by a Competing Need State.
Authors: Alhadeff Et al.
Cell 2018;173:140
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Dissociable Structural and Functional Hippocampal Outputs via Distinct Subiculum Cell Classes.
Authors: Cembrowski Et al.
Cell 2018;173:1280
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Medial Amygdala Kiss1 Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice.
Authors: Aggarwal Et al.
Neuroendocrinology 2018;108:172
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Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence.
Authors: Chai Et al.
Neuron 2017;95:531
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A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.
Authors: Francois Et al.
Neuron 2017;93:822
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Glutamatergic projections from the entorhinal cortex to dorsal dentate gyrus mediate context-induced reinstatement of heroin seeking.
Authors: Ge Et al.
Neuropsychopharmacology 2017;42:1860
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Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking.
Authors: Heinsbroek Et al.
J Neurosci 2017;37:757
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A tale of two circuits: CCKNTS neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions.
Authors: Roman Et al.
Neuroscience 2017;358:316
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Cortico-accumbens regulation of approach-avoidance behavior Is modified by experience and chronic pain.
Authors: Schwartz Et al.
Cell Rep 2017;19:1522
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Inhibiting medial septal cholinergic neurons with DREADD alleviated anxiety-like behaviors in mice.
Authors: Zhang Et al.
Neurosci Letts 2017;18:139
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Visuomotor coupling shapes the functional development of mouse visual cortex.
Authors: Attinger
Cell 2017;169(7):1291
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Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit.
Authors: Pina and Cunningham Et al.
Neurobiol Learn Mem 2017;137:83
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Using c-kit to genetically target cerebellar molecular layer interneurons in adult mice.
Authors: Amat
PLoS One 2017;12(6):e0179347
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Histamine modulation of the basal ganglia circuitry in the development of pathological grooming.
Authors: Rapanelli
Proc Natl Acad Sci U S A. 2017;114(25):6599
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Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.
Authors: D'Agostino Et al.
PLoS Biol 2016;5
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Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity.
Authors: Yuan and Grutzendler
J Neurosci 2016;36:632
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Neural activity promotes long-distance, target-specific regeneration of adult retinal axons.
Authors: Lim Et al.
Nat Neurosci 2016;19:1073
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Warm-Sensitive Neurons that Control Body Temperature.
Authors: Tan Et al.
Cell 2016;167:47
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Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit.
Authors: Pina and Cunningham
Neurobiol Learn Mem 2016;137:83
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DREADDS: Use and application in behavioral neuroscience.
Authors: Smith Et al.
Behav Neurosci 2016;130:137
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Reviews for Clozapine N-oxide
Average Rating: 4.5 (Based on 6 Reviews)
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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.
bleed assay
neuron silencer