From Wikipedia, the free encyclopedia
Clozapine N-oxide
Names
IUPAC name
3-chloro-6-(4-methyl-4-oxidopiperazin-4-ium-1-yl)-11H -benzo[b][1,4]benzodiazepine
Identifiers
ChEMBL
ChemSpider
ECHA InfoCard
100.164.243
UNII
InChI=1S/C18H19ClN4O/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
Key: OGUCZBIQSYYWEF-UHFFFAOYSA-N
C[N+]1(CCN(CC1)C2=NC3=C(C=CC(=C3)Cl)NC4=CC=CC=C42)[O-]
Properties
C 18 H 19 Cl N 4 O
Molar mass
342.83 g·mol−1
Hazards
GHS labelling :
Danger
H301 ,
H315 ,
H319 ,
H335
P261 ,
P264 ,
P270 ,
P271 ,
P280 ,
P301+P310 ,
P302+P352 ,
P304+P340 ,
P305+P351+P338 ,
P312 ,
P321 ,
P330 ,
P332+P313 ,
P337+P313 ,
P362 ,
P403+P233 ,
P405 ,
P501
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Clozapine N -oxide (CNO) is a synthetic
drug used mainly in
biomedical research as a
ligand to activate
DREADD receptors .
[1] Although CNO was initially believed to be biologically inert. However, it has been shown not to enter the brain after administration
[2] and to reverse metabolise in peripheral tissues to form clozapine. Clozapine can bind to a number of different serotonergic, dopaminergic and adrenergic receptors within the brain.
[3] Therefore, behavioural data using the CNO-DREADD system in neuroscience experiments have to be interpreted with caution.
[4]
Alternatives to CNO with more affinity, more inert character, and faster kinetics include Compound 21 (C21)
[5] and deschloroclozapine (DCZ).
[6]
References
^ Armbruster, B. N.; Li, X.; Pausch, M. H.; Herlitze, S.; Roth, B. L. (2007-03-02).
"Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand" . Proceedings of the National Academy of Sciences . 104 (12): 5163–5168.
Bibcode :
2007PNAS..104.5163A .
doi :
10.1073/pnas.0700293104 .
ISSN
0027-8424 .
PMC
1829280 .
PMID
17360345 .
^ Gomez, Juan L.; Bonaventura, Jordi; Lesniak, Wojciech; Mathews, William B.; Sysa-Shah, Polina; Rodriguez, Lionel A.; Ellis, Randall J.; Richie, Christopher T.; Harvey, Brandon K.; Dannals, Robert F.; Pomper, Martin G. (2017-08-04).
"Chemogenetics revealed: DREADD occupancy and activation via converted clozapine" . Science . 357 (6350): 503–507.
Bibcode :
2017Sci...357..503G .
doi :
10.1126/science.aan2475 .
ISSN
1095-9203 .
PMC
7309169 .
PMID
28774929 .
^ Manvich, Daniel F.; Webster, Kevin A.; Foster, Stephanie L.; Farrell, Martilias S.; Ritchie, James C.; Porter, Joseph H.; Weinshenker, David (2018-03-01).
"The DREADD agonist clozapine N -oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice" . Scientific Reports . 8 (1): 3840.
Bibcode :
2018NatSR...8.3840M .
doi :
10.1038/s41598-018-22116-z .
ISSN
2045-2322 .
PMC
5832819 .
PMID
29497149 .
^
This article incorporates
text available under the
CC BY 4.0 license. Ju, William (November 1, 2023). Neuroscience . Toronto: University of Toronto. 3.4 Chemogenic methods to examine the brain behaviour.
^ Bonaventura, Jordi; Eldridge, Mark A. G.; Hu, Feng; Gomez, Juan L.; Sanchez-Soto, Marta; Abramyan, Ara M.; Lam, Sherry; Boehm, Matthew A.; Ruiz, Christina; Farrell, Mitchell R.; Moreno, Andrea (2019-10-11).
"High-potency ligands for DREADD imaging and activation in rodents and monkeys" . Nature Communications . 10 (1): 4627.
Bibcode :
2019NatCo..10.4627B .
doi :
10.1038/s41467-019-12236-z .
ISSN
2041-1723 .
PMC
6788984 .
PMID
31604917 .
^ Nagai, Yuji; Miyakawa, Naohisa; Takuwa, Hiroyuki; Hori, Yukiko; Oyama, Kei; Ji, Bin; Takahashi, Manami; Huang, Xi-Ping; Slocum, Samuel T.; DiBerto, Jeffrey F.; Xiong, Yan (September 2020).
"Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys" . Nature Neuroscience . 23 (9): 1157–1167.
doi :
10.1038/s41593-020-0661-3 .
ISSN
1546-1726 .
PMID
32632286 .
S2CID
220375204 .