Clozapine N-oxide

SKU: orb1302814

Description

Clozapine N-oxide (CNO) is a brain-penetrant metabolite of clozapine and a potent agonist for DREADD receptors hM3Dq and hM4Di, widely used for chemogenetic neuronal manipulation in vivo. It also exhibits dopaminergic antagonist and muscarinic M4 receptor agonist activities, supporting its use in neuropharmacology research.

Research Area

Neuroscience, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 34233-69-7
• MW: 342.8
• Purity: >98%
• Formula: C₁₈H₁₉ClN₄O
• SMILES: CN1(=O)CCN(C=2C=3C(NC=4C(N2)=CC(Cl)=CC4)=CC=CC3)CC1
• Target: GPCR
• Solubility: Soluble in DMSO (up to 15 mg/ml) or in Ethanol (up to 3 mg/ml)

Bioactivity

• Target IC50:
  M4Di (human):8.1 nM (EC50)|CYP2C19:8.7 µM|CYP2B6:8.3 µM
• In Vivo:
  METHODS: To investigate potential effects on sleep, Clozapine N-oxide (1-10 mg/kg) was injected intraperitoneally into C57BL/6J mice. RESULTS: Clozapine N-oxide altered sleep in mice. Sleep was analyzed using electroencephalography (EEG) and electromyography (EMG), revealing dose-dependent suppression of rapid eye movement (REM) sleep, changes in EEG spectral power during non-rapid eye movement (NREM) sleep, and alterations in sleep structure. METHODS: To investigate the effects on reward-seeking behavior, Clozapine N-oxide (0.1-10 mg/kg) was administered intraperitoneally to C57BL6/JJcl mice. RESULTS: The off-target effects of commonly used doses of Clozapine N-oxide on motivated reward seeking were negligible.
• In Vitro:
  METHODS: hM4Di-transduced primary embryonic rat neuronal cultures were treated with Clozapine N-oxide (0.01-1000 nM), and activity on hM4Di receptors was detected by FLIPR assay. RESULTS: The EC50 value for Clozapine N-oxide was 8.1 nM. METHODS: WT and hM3Dq-transfected mouse embryoma cells ATDC5 were treated with Clozapine N-oxide (750 nM) to detect intracellular calcium signaling. RESULTS: Administration of Clozapine N-oxide resulted in immediate coordinated induction of single [Ca2+]i spines in hM3Dq-ATDC5 cells, and only spontaneous [Ca2+]i signaling was observed in Clozapine N-oxide-treated WT controls.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

hM3Dq, Inhibitor, G-protein, metabolite, mAChR, inhibit, Muscarinic acetylcholine receptor, muscarinic-M4, 5HTReceptor, 5HT Receptor, 5-HT, BBB, Clozapine, CLOZAPINE N OXIDE, CLOZAPINE NOXIDE, Clozapine N-oxide, CLOZAPINE N-OXIDE, DrugMetabolite, Drug Metabolite, DREADDs, Dopamine Receptor, Dopamine, DopamineReceptor

Compound Identifiers

PubChem CID

135445691