The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice
Open accessAbstract
Clozapine-N-oxide (CNO) has long been the ligand of choice for selectively activating Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). However, recent studies have challenged the long-held assertion that CNO is otherwise pharmacologically inert. The present study aimed to 1) determine whether CNO is reverse-metabolized to its parent compound clozapine in mice (as has recently been reported in rats), and 2) determine whether CNO exerts clozapine-like interoceptive stimulus effects in rats and/or mice. Following administration of 10.0 mg/kg CNO, pharmacokinetic analyses replicated recent reports of back-conversion to clozapine in rats and revealed that this phenomenon also occurs in mice. In rats and mice trained to discriminate 1.25 mg/kg clozapine from vehicle, CNO (1.0–20.0 mg/kg) produced partial substitution for the clozapine stimulus on average, with full substitution being detected in some individual animals of both species at doses frequently used to activate DREADDs. The present demonstration that CNO is converted to clozapine and exerts clozapine-like behavioral effects in both mice and rats further emphasizes the need for appropriate control groups in studies employing DREADDs, and highlights the utility of the drug discrimination procedure as a tool with which to screen the off-target effects of novel DREADD agonists.
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Chemogenetics revealed: DREADD occupancy and activation via converted clozapine
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Jendryka, M., Palchaudhuri, M., Ursu, D., van der Veen, B., Liss, B., Kätzel, D., Nissen, W., & Pekcec, A. (2019) · Scientific Reports · doi:10.1038/s41598-019-41088-2 · Cited by 296
Normal cognitive and social development require posterior cerebellar activity
Badura, A., Verpeut, J. L., Metzger, J. W., Pereira, T. D., Pisano, T. J., Deverett, B., Bakshinskaya, D. E., & Wang, S. S.-H. (2018) · eLife · doi:10.7554/elife.36401 · Cited by 205
Fogaça, M. V., Wu, M., Li, C., Li, X.-Y., Picciotto, M. R., & Duman, R. S. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00916-y · Cited by 129
Neuronal activity increases translocator protein (TSPO) levels
Notter, T., Schalbetter, S. M., Clifton, N. E., Mattei, D., Richetto, J., Thomas, K., Meyer, U., & Hall, J. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0745-1 · Cited by 118
Rogers-Carter, M. M., Djerdjaj, A., Gribbons, K. B., Varela, J. A., & Christianson, J. P. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0316-19.2019 · Cited by 79
Metadata
- Authors
- Manvich, D. F., Webster, K. A., Foster, S. L., Farrell, M. S., Ritchie, J. C., Porter, J. H., & Weinshenker, D.
- Venue
- Scientific Reports
- Published
- 2018-03-01
- Volume
- 8
- Issue
- 1
- Pages
- 3840-3840
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2804376135
- Cited by
- 367
- References
- 21
- FWCI
- 14.79
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. https://app.cochat.ai/papers/10.1038/s41598-018-22116-z
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- Manvich, D. F., Webster, K. A., Foster, S. L., Farrell, M. S., Ritchie, J. C., Porter, J. H., & Weinshenker, D. (2018). 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. https://doi.org/10.1038/s41598-018-22116-z
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
