Clozapine N-oxide

Catalog # Availability Size / Price Qty
Clozapine N-oxide | CAS No. 34233-69-7 | DREADD Activators
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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%

Product Details
Citations (53)
Supplemental Products
Reviews (6)

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

Soluble to 20 mM in DMSO
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.

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

  1. 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
  2. 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
  3. Identification of a population of peripheral sensory neurons that regulates blood pressure.
    Authors: Morelli Et al.
    Cell Rep  2021;35
  4. Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons.
    Authors: Maldonado Et al.
    Curr Biol  2021;31:322
  5. Chronic postnatal chemogenetic activation of forebrain excitatory neurons evokes persistent changes in mood behavior
    Authors: Pati Et al.
    ELife  2020;9
  6. 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
  7. 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
  8. Brainstem neurons that command mammalian locomotor asymmetries.
    Authors: Cregg Et al.
    Nat Neurosci  2020;23:730
  9. Anatomically and functionally distinct locus coeruleus efferents mediate opposing effects on anxiety-like behavior
    Authors: Borodovitsyna Et al.
    Neurobiology of Stress  2020;13
  10. 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
  11. Astroglia in lateral habenula is essential for antidepressant efficacy of light
    Authors: Delcourte Et al.
    BioRXiv - not yet peer reviewed  2020;
  12. Sodium regulates clock time and output via an excitatory GABAergic pathway.
    Authors: Gizowski & Bourque Et al.
    Nature  2020;
  13. Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst.
    Authors: Ma Et al.
    J Physiol  2019;597:4851
  14. Prefrontal Theta Oscillations Promote Selective Encoding of Behaviorally Relevant Events.
    Authors: Jarovi Et al.
    Eneuro  2019;5
  15. Galanin Neurons Unite Sleep Homeostasis and α2-Adrenergic Sedation
    Authors: Ma Et al.
    Curr Biol  2019;29:3315
  16. Maladaptive Downregulation of Autonomous Subthalamic Nucleus Activity following the Loss of Midbrain Dopamine Neurons
    Authors: McIver Et al.
    Cell Rep  2019;28:992
  17. Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference
    Authors: Nam Et al.
    Cell Rep  2019;28:1154
  18. Routing Hippocampal Information Flow through Parvalbumin Interneuron Plasticity in Area CA2.
    Authors: Nasrallah Et al.
    Cell Rep  2019;27:86
  19. Chemogenetic Activation of Adrenocortical Gq Signaling Causes Hyperaldosteronism and Disrupts Functional Zonation.
    Authors: Taylor Et al.
    J Clin Invest  2019;130:83
  20. Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.
    Authors: Weiner Et al.
    Nat Commun  2019;10:2477
  21. 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
  22. A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics.
    Authors: Meira Et al.
    Nat.Commun.  2018;9:4163
  23. The role of calretinin-expressing granule cells in olfactory bulb functions and odor behavior.
    Authors: Hardy Et al.
    Sci Rep  2018;8:9385
  24. Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures.
    Authors: Berglind Et al.
    Sci Rep  2018;8:5669
  25. Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain.
    Authors: Jiang Et al.
    Neurosci Letts  2018;671:7
  26. A circuit from hippocampal CA2 to lateral septum disinhibits social aggression.
    Authors: Leroy Et al.
    Nature  2018;564:213
  27. Parallel Arousal Pathways in the Lateral Hypothalamus.
    Authors: Heiss Et al.
    Eneuro  2018;5
  28. 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
  29. Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation.
    Authors: Gelegen Et al.
    Curr Biol  2018;28:580
  30. 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
  31. 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
  32. The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study.
    Authors: Terburg Et al.
    Cell  2018;175:723
  33. Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement.
    Authors: Adamsky Et al.
    Cell  2018;174:59
  34. A Neural Circuit for the Suppression of Pain by a Competing Need State.
    Authors: Alhadeff Et al.
    Cell  2018;173:140
  35. Dissociable Structural and Functional Hippocampal Outputs via Distinct Subiculum Cell Classes.
    Authors: Cembrowski Et al.
    Cell  2018;173:1280
  36. Medial Amygdala Kiss1 Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice.
    Authors: Aggarwal Et al.
    Neuroendocrinology  2018;108:172
  37. Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence.
    Authors: Chai Et al.
    Neuron  2017;95:531
  38. A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.
    Authors: Francois Et al.
    Neuron  2017;93:822
  39. 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
  40. Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking.
    Authors: Heinsbroek Et al.
    J Neurosci  2017;37:757
  41. 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
  42. Cortico-accumbens regulation of approach-avoidance behavior Is modified by experience and chronic pain.
    Authors: Schwartz Et al.
    Cell Rep  2017;19:1522
  43. Inhibiting medial septal cholinergic neurons with DREADD alleviated anxiety-like behaviors in mice.
    Authors: Zhang Et al.
    Neurosci Letts  2017;18:139
  44. Visuomotor coupling shapes the functional development of mouse visual cortex.
    Authors: Attinger
    Cell  2017;169(7):1291
  45. 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
  46. Using c-kit to genetically target cerebellar molecular layer interneurons in adult mice.
    Authors: Amat
    PLoS One  2017;12(6):e0179347
  47. 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
  48. Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.
    Authors: D'Agostino Et al.
    PLoS Biol  2016;5
  49. Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity.
    Authors: Yuan and Grutzendler
    J Neurosci  2016;36:632
  50. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons.
    Authors: Lim Et al.
    Nat Neurosci  2016;19:1073
  51. Warm-Sensitive Neurons that Control Body Temperature.
    Authors: Tan Et al.
    Cell  2016;167:47
  52. Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit.
    Authors: Pina and Cunningham
    Neurobiol Learn Mem  2016;137:83
  53. 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

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CNO in DREADD pain targeted Mice
By Anonymous on 12/15/2017

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

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

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

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

bleed assay

neuron silencer
By Anonymous on 07/17/2017

neuron silencer

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