Chemistry:Clozapine N-oxide
From HandWiki
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| IUPAC name
3-chloro-6-(4-methyl-4-oxidopiperazin-4-ium-1-yl)-11H-benzo[b][1,4]benzodiazepine
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3D model (JSmol)
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PubChem CID
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| Properties | |
| C18H19ClN4O | |
| Molar mass | 342.83 g·mol−1 |
| Hazards | |
| GHS pictograms |  
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| GHS Signal word | Danger |
| H301, H315, H319, H335 | |
| P261, P264, P270, P271, P280, P301+310, P302+352, P304+340, P305+351+338, P312, P321, P330, P332+313, P337+313, P362, P403+233, P405, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
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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" (in en). Proceedings of the National Academy of Sciences 104 (12): 5163–5168. doi:10.1073/pnas.0700293104. ISSN 0027-8424. PMID 17360345. Bibcode: 2007PNAS..104.5163A.
- ↑ Gomez, Juan L.; Bonaventura, Jordi; Lesniak, Wojciech; Mathews, William B.; Sysa-Shah, Polina; Rodriguez, Lionel A.; Ellis, Randall J.; Richie, Christopher T. et al. (2017-08-04). "Chemogenetics revealed: DREADD occupancy and activation via converted clozapine". Science 357 (6350): 503–507. doi:10.1126/science.aan2475. ISSN 1095-9203. PMID 28774929. Bibcode: 2017Sci...357..503G.
- ↑ 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" (in en). Scientific Reports 8 (1): 3840. doi:10.1038/s41598-018-22116-z. ISSN 2045-2322. PMID 29497149. Bibcode: 2018NatSR...8.3840M.
- ↑
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. et al. (2019-10-11). "High-potency ligands for DREADD imaging and activation in rodents and monkeys" (in en). Nature Communications 10 (1): 4627. doi:10.1038/s41467-019-12236-z. ISSN 2041-1723. PMID 31604917. Bibcode: 2019NatCo..10.4627B.
- ↑ Nagai, Yuji; Miyakawa, Naohisa; Takuwa, Hiroyuki; Hori, Yukiko; Oyama, Kei; Ji, Bin; Takahashi, Manami; Huang, Xi-Ping et al. (September 2020). "Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys" (in en). Nature Neuroscience 23 (9): 1157–1167. doi:10.1038/s41593-020-0661-3. ISSN 1546-1726. PMID 32632286. https://www.nature.com/articles/s41593-020-0661-3.
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