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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.

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

    ‘Inhibitory’ (Gi- coupled) DREADDs:

    CNO also activates the inhibitory hM4Di and hM2Di Gi-coupled DREADDs.

    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 suggest that systemically administered CNO does not readily cross the blood-brain-barrier in vivo, and converts to clozapine which activates DREADDs. Care must be taken in experimental design and proper controls should be incorporated.


    Our stability studies have shown that CNO dihydrochloride is easier to solubilize and handle, and is more stable in solution than 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 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

  • 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

    • Hydroscopic solid, 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.
    • Always store solutions at -20°C.

  • 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)

  • Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects.

    Strange PG (2001) Pharmacol Rev 53(1) : 119-33.
    PubMedID: 11171942
  • Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.

    Sunahara RK et al (1991) Nature 350(6319) : 614-9.
    PubMedID: 1826762
  • 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
Support & Resources

Reviews

  • Verified customer, The University of Tennessee Health Science Center (UTHSC)

    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."