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Clozapine N-oxide (CNO) dihydrochloride (water soluble)

(HB6149)
Data

Product overview

  • Name
    Clozapine N-oxide (CNO) dihydrochloride (water soluble)
  • Short description
    Dihydrochloride salt of CNO - the prototypical DREADD activator
  • Biological description

    Clozapine N-oxide dihydrochloride (CNO) is the dihydrochloride salt of CNO which is the prototypical chemical DREADDs activator. It is a metabolite of clozapine.


    ‘Excitatory’ (Gq- coupled) DREADDs:

    CNO activates the excitatory Gq- coupled DREADDs: hM3Dq, hM1Dq and hM5Dq (pEC50 values are 7.26 and 8.61 at hM3Dq and hM1Dq respectively).

    The hM3Dq DREADD is typically used for enhancing neuronal firing and activity (Gq- signaling in neuronal and non-neuronal cells).

    ‘Inhibitory’ (Gi- coupled) DREADDs:

    CNO also activates the inhibitory hM4Di and hM2Di Gi-coupled DREADDs (pEC50 = 6.89 at hM4Di).

    The hM4Di DREADD is the most commonly used inhibitory DREADD and is used for neuronal silencing.

    Gs and β-arrestin coupled DREADDs:

    CNO also activates the Gs- coupled DREADD (GsD) and the β-arrestin preferring DREADD: rM3Darr (Rq(R165L).


    In the literature, CNO has been administered intraperitoneally (i.p.), subcutaneously, directly infused intracranially, via drinking water, osmotic mini-pump and recently via eye drops. See our Technical review (table 3) for example administration methods and doses.


    Recent findings (Gomez et al 2016) suggest that systemically administered CNO does not readily cross the blood-brain-barrier in vivo, and converts to clozapine which activates DREADDs. Therefore care must be taken in experimental design and proper controls should be incorporated, for example, the use of non-DREADD expressing animals may be appropriate (see Mahler and Aston-Jones (2018)).

    CNO has proved to be an effective actuator of muscarinic DREADDs and provided controls are in place, will continue to be an excellent tool. Compound 21 (DREADD agonist 21) represents an alternative to CNO for in vivo studies in which metabolic conversion of CNO to clozapine is an issue (Thompson et al 2019).


    Our stability studies have shown that CNO dihydrochloride is easier to solubilize and handle and have found that this product does not precipitate in solution unlike the freebase form of CNO (which, due to its inherent chemical properties requires careful handling and has been shown in the literature to precipitate in aqueous solution under certain conditions).

  • Alternative names
    CNO dihydrochloride, CNO.2HCl
  • Biological action
    Activator
  • Purity
    >98%
  • Customer comments

    We have been using Clozapine N-oxide (CNO) dihydrochloride (CNO.2HCl) from Hello Bio. We are fully satisfied with this product: it is readily water soluble and stable. We have administered CNO-2HCl to animals via IP injection and intracranial microinjection; and we have observed CNO-induced cellular and behavioral effects fully consistent with its expected activation of DREADD receptors." Verified customer, UTHSC

    Great product. Great company and product. Better pricing & similar quality compared to the most of the other companies. We used CNO dihydrochloride for both i.p. and drinking water delivery, and it worked fine. Nice service. Verified customer, University of Minnesota

    Works as expected, and significantly cheaper than alternatives. Will use this for future CNO purchases Verified customer, UCSF

  • Citations

Properties

  • Chemical name
    8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine dihydrochloride
  • Molecular Weight
    415.74
  • Chemical structure
    Clozapine N-oxide dihydrochloride
  • Molecular Formula
    C18H19ClN4O.2HCl
  • SMILES
    ClC(C=C1)=CC2=C1NC(C=CC=C3)=C3C(N4CC[N+](C)([O-])CC4)=N2.Cl.Cl
  • Source
    Synthetic
  • InChi
    InChI=1S/C18H19ClN4O.2ClH/c1-23(24)10-8-22(9-11-23)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18;;/h2-7,12,20H,8-11H2,1H3;2*1H
  • InChiKey
    MBRGKRXDVKTUPT-UHFFFAOYSA-N
  • Appearance
    Orange solid

Applications

Storing and Using Your Product

  • Storage instructions
    -20°C
  • Solubility overview
    Soluble in water (100 mM). Always store solutions at -20°C.
  • Handling

    Storage of solid

    • Store at -20°C.
    • Please note that the compound is a hydroscopic solid and contact with air may cause material to become sticky. Product performance should not be affected but we recommend storing the material in a sealed jar.

    Storage of solutions

    • Make up solutions and use immediately.
    • If storage of solutions is required, you should aliquot out the solution into tightly sealed vials and store at -20°C and store these for up to one month.
    • Allow the product to equilibrate to RT for at least one hour before opening and using.

    Storage of solutions at room temperature

    • We recommend only keeping solutions at room temperature (25°C) for a few days as our studies have shown that after 96 hours the purity of the compound in solution drops to ~95% and will continue to drop over time.
  • Important
    This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use

References for Clozapine N-oxide (CNO) dihydrochloride (water soluble)

  • Novel designer receptors to probe GPCR signaling and physiology.

    Wess et al (2013) Trends Pharmacol Sci. 34(7) : 385-92
    PubMedID: 23769625
  • Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.

    Arbruster et al (2007) Proc Natl Acad Sci U S A 104(12) : 5163-8
    PubMedID: 17360345
  • Differential regulation of rat 5-HT2A and 5-HT2C receptors after chronic treatment with clozapine, chlorpromazine and three putative atypical antipsychotic drugs.

    Kuoppamã?ki M et al (1995) Neuropsychopharmacology 13(2) : 139-50.
    PubMedID: 8597525
  • Chemogenetics revealed: DREADD occupancy and activation via converted clozapine.

    Gomez et al (2017) Science 357(6350) : 503-507
    PubMedID: 28774929
  • CNO Evil? Considerations for the Use of DREADDs in Behavioral Neuroscience.

    Mahler and Aston-Jones (2018) Neuropsychopharmacology doi: 10.1038 : /npp.2016.251
    PubMedID: 29303143
  • DREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDs in Vitro and in Vivo

    Thompson et al (2018) ACS Pharmacol. Transl. Sci. 10.1021 : /acsptsci.8b00012
Our products in action
The following papers have cited the use of Clozapine N-oxide (CNO) dihydrochloride (water soluble) (HB6149) from Hello Bio. If you have published a paper using this product, and it is not shown here, then please tell us! We will send you a free gift as a thank you!
  • cAMP-producing chemogenetic activation of indirect pathway striatal projection neurons and the downstream effects on the globus pallidus and subthalamic nucleus in freely moving mice.

    Bouabid and Zhou (2018) J Neurochem doi: 10.1111/jnc.14331. : [Epub ahead of print]
    PubMedID: 29500819
Support & Resources

Reviews

  • Verified customer, University of Minnesota

    Great product. Great company and product. Better pricing & similar quality compared to the most of the other companies. We used CNO dihydrochloride for both i.p. and drinking water delivery, and it worked fine. Nice service.
  • Verified customer, UCSF

    Works as expected, and significantly cheaper than alternatives. Will use this for future CNO purchases
  • Verified customer, UCLA

    Good.
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