Clozapine N-oxide (dihydrochloride)
Clozapine N-oxide dihydrochloride is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist. Clozapine N-oxide dihydrochloride activates the DREADD receptor hM3Dq and hM4Di. Clozapine N-oxide dihydrochloride cannot cross the blood-brain barrier[1][2][3][4]. Clozapine is a potent dopamine antagonist and also a potent and selective muscarinic M4 receptor (EC50=11 nM) agonist[5][6].
Product Specifications
CAS Number
[2250025-93-3]
UNSPSC
12352005
Hazard Statement
H301, H336
Target
Dopamine Receptor; Drug Metabolite; mAChR
Type
Reference compound
Related Pathways
GPCR/G Protein; Metabolic Enzyme/Protease; Neuronal Signaling
Applications
Neuroscience-Neuromodulation
Field of Research
Neurological Disease
Assay Protocol
https://www.medchemexpress.com/clozapine-n-oxide-dihydrochloride.html
Purity
99.74
Solubility
DMSO : ≥ 200 mg/mL|H2O : 100 mg/mL (ultrasonic)
Smiles
C[N+]1([O-])CCN(C2=NC3=CC(Cl)=CC=C3NC4=CC=CC=C42)CC1.[H]Cl.[H]Cl
Molecular Formula
C18H21Cl3N4O
Molecular Weight
415.74
Precautions
H301, H336
References & Citations
[1]Wess J, et al. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul;34 (7) :385-92.|[2]Manvich DF, et al. The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Sci Rep. 2018 Mar 1;8 (1) :3840.|[3]van der Peet PL, et al. Gram scale preparation of clozapine N-oxide (CNO), a synthetic small molecule actuator for muscarinic acetylcholine DREADDs. MethodsX. 2018 Mar 23;5:257-267.|[4]Silva RR, et al. Evaluation of Functional Selectivity of Haloperidol, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor. Front Pharmacol. 2019 Jun 4;10:628.|[5]Zorn SH, et al. Clozapine is a potent and selective muscarinic M4 receptor agonist. Eur J Pharmacol. 1994 Nov 15;269 (3) :R1-2.|[6]Joseph Cichon, et al. Branch-specific dendritic Ca (2+) spikes cause persistent synaptic plasticity. Nature. 2015 Apr 9;520 (7546) :180-5.
Shipping Conditions
Room Temperature
Storage Conditions
4°C (Powder, stored under nitrogen)
Scientific Category
Reference compound1
Clinical Information
No Development Reported
Isoform
MAChR3; mAChR4
Citation 01
BioRxiv. 2025 Oct 9.|Cell Stem Cell. 2025 May 1;32 (5) :778-794.e10.|Cells. 2022 Dec 21;12 (1) :26.|Exp Neurol. 2024 Jul:377:114801.|Fundam Res. 2024 Mar 19.|Int Immunopharmacol. 2025 Sep 6:165:115494.|iScience. 2022 Dec 20;26 (1) :105840.|Mol Psychiatry. 2025 Oct 24.|Pharmacol Biochem Behav. 2025 Dec:257:174114.|Pharmacol Res. 2023 May:191:106773.|ACS Infect Dis. 2025 Jun 13;11 (6) :1528-1538.|Acta Pharm Sin B. 2024 Nov;14 (11) :4789-4805.|Acta Pharmacol Sin. 2023 Jul;44 (7) :1337-1349.|Acta Pharmacol Sin. 2025 Apr;46 (4) :904-921.|Acta Pharmacol Sin. 2025 May 6.|Acta Physiol. 2023 Mar;237 (3) :e13917.|Actas Esp Psiquiatr. 2025 May;53 (3) :504-515.|Adv Sci (Weinh) . 2023 Aug;10 (22) :e2301110.|Adv Sci (Weinh) . 2023 Jun;10 (16) :e2204824.|Adv Sci (Weinh) . 2024 Aug 9:e2400253.|Adv Sci (Weinh) . 2024 Dec 11:e2410728.|Adv Sci (Weinh) . 2025 Apr 30:e2502421.|Adv Sci (Weinh) . 2025 Apr;12 (14) :e2414723.|Adv Sci (Weinh) . 2025 Jun 30:e03017.|Adv Sci (Weinh) . 2025 Mar 31:e2416348.|Adv Sci (Weinh) . 2025 May;12 (18) :e2412822.|Am J Physiol Endocrinol Metab. 2025 Aug 1;329 (2) :E254-E265.|Anesthesiology. 2021 Oct 1;135 (4) :633-648.|Anesthesiology. 2021 Sep 1;135 (3) :463-481.|Biol Psychiatry. 2017 May 1;81 (9) :737-747.|bioRxiv. 2023 Oct 9.|bioRxiv. 2024 Apr 29.|bioRxiv. 2024 July 23.|bioRxiv. 2025 August 25.|bioRxiv. 2025 Sep 5.|Brain Behav Immun. 2023 Aug:112:96-117.|Brain Commun. 2022 Aug 30;4 (5) :fcac219.|Brain Stimul. 2023 Dec 23;17 (1) :49-64.|Cell Metab. 2022 Feb 1;34 (2) :285-298.e7.|Cell Rep. 2021 Mar 23;34 (12) :108889.|Cell Rep. 2023 Dec 3;42 (12) :113551.|Cell Rep. 2023 Mar 21;42 (4) :112290.|Cell Rep. 2024 Dec 10;43 (12) :115074.|Cell Rep. 2024 Feb 17;43 (2) :113804.|Cell Rep. 2024 Nov 19;43 (12) :114983.|Cell Rep. 2024 Oct 3;43 (10) :114800.|Cell. 2025 Sep 18;188 (19) :5175-5193.e21.|CNS Neurosci Ther. 2023 Jan;29 (1) :390-401.|CNS Neurosci Ther. 2024 Jan;30 (1) :e14554.|CNS Neurosci Ther. 2024 Jun;30 (6) :e14782.|CNS Neurosci Ther. 2024 Mar;30 (3) :e14675.|Commun Biol. 2021 Sep 16;4 (1) :1088.|Commun Biol. 2023 Jan 14;6 (1) :50.|Ecotoxicol Environ Saf. 2023 Jun 29:262:115205.|Ecotoxicol Environ Saf. 2024 Nov 30:289:117392.|Elife. 2021 Sep 16;10:e67535.|Elife. 2024 May 29.|Elife. 2024 Nov 20:13:RP97954.|Exp Neurol. 2025 May:387:115193.|Exp Neurol. 2025 Oct 1:395:115489.|FASEB J. 2020 Sep;34 (9) :11913-11924.|FASEB J. 2025 Sep 15;39 (17) :e71015.|Front Cell Neurosci. 2021 Apr 30:15:671473.|Front Neurosci. 2020 Jul 14;14:646.|iScience. 2023 Aug 14;26 (9) :107486.|iScience. 2023 Oct 23;26 (11) :108306.|iScience. 2024 Oct 24;27 (11) :111251.|iScience. 2025 Nov 22.|J Adv Res. 2025 Oct 12:S2090-1232 (25) 00782-9.|J Affect Disord. 2025 Mar 1:372:149-159.|J Neuroinflammation. 2022 Jun 27;19 (1) :166.|J Neuroinflammation. 2022 May 27;19 (1) :123.|J Neuroinflammation. 2025 Oct 2;22 (1) :222.|J Neuropathol Exp Neurol. 2023 Aug 21;82 (9) :806-813.|J Neurosci. 2021 Dec 1;41 (48) :9988-10003.|J Neurosci. 2024 Jul 17:e0740242024.|J Neurosci. 2024 May 14:e0222242024.|J Neurosci. 2025 Aug 26:e1316242025.|J Psychiatry Neurosci. 2024 May 30;49 (3) :E192-E207.|Life Metab. 2023 Feb 4;2 (1) :load004.|Life Sci. 2020 Oct 1;258:118099.|Mol Neurobiol. 2025 Mar;62 (3) :2817-2834.|Mol Neurobiol. 2025 Nov 17;63 (1) :63.|Nat Commun. 2020 Jun 5;11 (1) :2847. |Nat Commun. 2020 Nov 27;11 (1) :6045.|Nat Commun. 2022 Apr 25;13 (1) :2233.|Nat Commun. 2023 Apr 17;14 (1) :2182.|Nat Commun. 2024 Oct 5;15 (1) :8632.|Nat Commun. 2025 Jul 25;16 (1) :6871.|Nat Commun. 2025 May 16;16 (1) :4560.|Nat Neurosci. 2022 Dec;25 (12) :1639-1650.|Nat Neurosci. 2023 Apr;26 (4) :542-554.|Nat Neurosci. 2025 Jul;28 (7) :1404-1417.|Neural Regen Res. 2024 Feb;19 (2) :425-433.|Neural Regen Res. 2025 Jun 19.|Neurobiol Dis. 2023 Jun 15:182:106155.|Neurobiol Stress. 2022 Sep 22:21:100492.|Neuron. 2024 Apr 16:S0896-6273 (24) 00235-6.|Neuron. 2025 Jul 29:S0896-6273 (25) 00509-4.|Neuropharmacology. 2018 Jun:135:474-486.|Neuropharmacology. 2025 Apr 1:267:110301.|Neuropsychopharmacology. 2023 Sep;48 (10) :1509-1519.|Neuropsychopharmacology. 2024 May;49 (6) :961-973.|Neurosci Bull. 2021 May;37 (5) :597-610.|Neurosci Bull. 2021 Sep;37 (9) :1325-1338.|Neurosci Bull. 2023 Apr;39 (4) :617-630.|Neurosci Bull. 2023 Jun;39 (6) :962-972.|Neuroscience. 2019 Aug 21:414:299-310.|P Natl Acad Sci USA. 13, 2021 118 (28) e2103505118.|PLoS Biol. 2025 Jul 14;23 (7) :e3003272.|PLoS Biol. 2025 May 20;23 (5) :e3003170.|Proc Natl Acad Sci U S A. 2019 Aug 13;116 (33) :16583-16592.|Proc Natl Acad Sci U S A. 2023 May 9;120 (19) :e2215590120.|Prog Neuropsychopharmacol Biol Psychiatry. 2022 Apr 20:115:110496.|Psychoneuroendocrinology. 2020 Jul;117:104690.|Psychopharmacology (Berl) . 2024 May 14.|Res Sq. 2024 Jul 10.|Research (Wash D C) . 2025 Sep 25.|Research (Wash D C) . 2025 Sep 25:2025:0897.|Research Square Preprint. 2021 Mar.|Research Square Preprint. 2023 Sep 22.|Research Square Print. September 6th, 2022|Signal Transduct Target Ther. 2025 Nov 24;10 (1) :387.|SSRN. 2023 Jul 18.|SSRN. 2024 Oct 30.|Theranostics. 2023 May 11;13 (9) :2946-2961.|Theranostics. 2024 Jan 1;14 (2) :480-495.|Transl Psychiatry. 2020 Jun 20;10 (1) :202.|University of British Columbia. 2025.|University of Maryland. 2025.|University of Michigan, Horace H. Rackham School of Graduate Studies. 2018 Oct.
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