Clozapine N-oxide (CNO) dihydrochloride (water soluble)(HB6149)
NameClozapine N-oxide (CNO) dihydrochloride (water soluble)
Short descriptionDihydrochloride salt of CNO - the prototypical DREADD activator
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 or osmotic mini-pump. 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 freebase (HB1807) 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 namesCNO dihydrochloride
Chemical name8-Chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine dihydrochloride
Other Non-CNO DREADD activators available:
- Water soluble Compound 21 (DREADD agonist 21) hydrochloride has minimal off-target activity and is indicated not to metabolize to clozapine. The freebase Compound 21 (DREADD agonist 21) is also available.
- Perlapine hydrochloride (water soluble) is a potent and selective hM3Dq DREADD agonist. Perlapine freebase is also available.
- Salvinorin B (SALB) Salvinorin B (SALB) potently activates the inhibitory KORD DREADD to induce neuronal inhibition.
Storing and Using Your Product
Storage instructionsRoom temperature
Solubility overviewSoluble in water (100 mM)
HandlingHydroscopic 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.
ImportantThis 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) : 503-507PubMedID: 28774929