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Blockage of 5HT2Cserotonin receptors by fluoxetine (Prozac)
Open accessAbstract
Fluoxetine (Prozac) inhibited the membrane currents elicited by serotonin (5-hydroxytryptamine; 5HT) in Xenopus oocytes expressing either cloned 5HT 2C receptors or 5HT receptors encoded by rat cortex mRNA. Responses of 5HT 2C receptors, elicited by nM concentrations of 5HT, were rapidly and reversibly blocked by micromolar concentrations of fluoxetine. For responses elicited by 1 μM 5HT, the IC 50 of fluoxetine inhibition was ≈20 μM. In accord with the electrophysiological results, fluoxetine inhibited the binding of [3 H]5HT to 5HT 2C receptors expressed in HeLa cells (Ki≈ 65–97 nM), and the binding to 5HT receptors in rat cortex membranes was also inhibited but less efficiently (Ki≈ 56 μM). Our results show that fluoxetine is a competitive and reversible antagonist of 5HT 2C receptors and suggest that some therapeutic effects of fluoxetine may involve blockage of 5HT receptors, in addition to its known blockage of 5HT transporters. Similar work may help to design more selective compounds for use in the treatment of brain disorders.
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Yung-Chi, C., & Prusoff, W. H. (1973) · Biochemical Pharmacology · doi:10.1016/0006-2952(73)90196-2 · Cited by 12,922
Inositol trisphosphate and calcium signalling
Berridge, M. J. (1993) · Nature · doi:10.1038/361315a0 · Cited by 6,545
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Metadata
- Authors
- Ni, Y. G., & Miledi, R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-03-04
- Volume
- 94
- Issue
- 5
- Pages
- 2036-2040
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2164650786
- Cited by
- 177
- References
- 2
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Ni, Y. G., & Miledi, R. (1997). Blockage of 5HT2Cserotonin receptors by fluoxetine (Prozac). Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.5.2036
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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.
