34233-69-7 Usage
Description
Clozapine N-oxide (CNO) is an inactive metabolite of the clozapine drug, which serves as a synthetic ligand for engineered human muscarinic receptors, known as DREADDs (designer receptors exclusively activated by designer drugs). It is a yellow solid that activates G-protein-coupled receptors (GPCRs) and elicits clozapine-like effects upon metabolic conversion. The conversion of clozapine to CNO enhances its passage through the blood-brain barrier, making it a valuable compound for various applications in neuroscience and pharmacology.
Uses
1. Used in Neuroscience Research:
Clozapine N-oxide is used as an activator for human M4 muscarinic (hM4Di) receptors in the primary motor cortex. This application allows researchers to study the role of these receptors in motor control and other related functions.
2. Used in Chemogenetic Manipulation:
CNO is used for inducing in vivo chemogenetic manipulation, specifically in Th-cre transgenic mice. This application helps researchers understand the effects of specific genetic modifications on locomotor activity and other behavioral aspects in these mice.
3. Used in Behavioral Testing in Mice:
Clozapine N-oxide is used in behavioral testing for mice, providing insights into the effects of the compound on various aspects of mouse behavior and its potential applications in studying neurological disorders.
4. Used in Cell Stimulation:
CNO is used for stimulating HEK293 cells, a widely used cell line for various research applications. This use allows researchers to study the effects of CNO on cellular processes and its potential role in cell signaling.
5. Used as a 5-HT2 Antagonist:
Clozapine N-oxide is a major metabolite of clozapine that can be monitored by high-performance liquid chromatography (HPLC). It possesses little or no activity towards serotonin receptors, making it a useful compound for studying the specific effects of clozapine without the interference of serotonin receptor activation.
6. Used in Drug Delivery Systems:
Clozapine N-oxide may be used to control grafted human pluripotent stem cell-derived neurons engineered to express DREADDs. This application could potentially enhance the delivery, bioavailability, and therapeutic outcomes of CNO in various neurological applications.
7. Used in Various Other Applications:
Clozapine N-oxide has numerous other applications in neuroscience, pharmacology, and other fields, making it a versatile compound for research and potential therapeutic development.
Biochem/physiol Actions
5-HT2 serotonin receptor antagonist; major metabolite of clopazine that can be monitored by HPLC.
References
1) Eiermann?et al.?(1997),?The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine; Br. J. Clin. Pharmacol.,?44?439
2) Armbruster?et al.?(2007),?Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand; Proc. Natl. Acad. Sci. USA,?104?5163
3) Chen?et al.?(2016),?Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson’s Disease; Cell Stem Cell,?18?817
4) Vazey and Aston-Jones (2014),?Designer receptors: therapeutic adjuncts to cell replacement therapy in Parkinson’s disease: J. Clin. Invest.,?124?2858
5) Gomez?et al.?(2017)?Chemogenetics revealed: DREADD occupancy and activation via converted clozapine; Science?357?503
6) Marcinkiewcz?et al. (2016)?Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala; Nature?537?97
Check Digit Verification of cas no
The CAS Registry Mumber 34233-69-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,4,2,3 and 3 respectively; the second part has 2 digits, 6 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 34233-69:
(7*3)+(6*4)+(5*2)+(4*3)+(3*3)+(2*6)+(1*9)=97
97 % 10 = 7
So 34233-69-7 is a valid CAS Registry Number.
InChI:InChI=1/C18H19ClN4O/c1-21-8-10-22(11-9-21)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)23(18)24/h2-7,12,24H,8-11H2,1H3
