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Sub-anesthetic concentrations of (R, S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors
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The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC(50) = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤ 1 μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [(125)I]-α-bungarotoxin and [(3)H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC(50) 3.1 and 9.1 μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC(50) >100 μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [(3)H]-MK-801. The calculated K(i) values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and>100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug.
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“(2R,6R)-HNK has a binding affinity (Ki) and IC50 greater than 100 μM with 24% inhibition at 100 μM, and fails to impact NMDA-evoked currents in CA1 interneurons (Moaddel et al., 2013; Morris et al., 2017; Zanos et al., 2016).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Moaddel et al., 2013
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“its inability to displace MK-801 binding to NMDARs (10 μM).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Moaddel et al., 2013
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“Important for the mechanism of action of (2R,6R)-HNK as an antidepressant (and thus ketamine’s action) is the fact that at relevant concentrations (i.e., 10 mg/kg or brain Cmax = ~10 μmol/kg in mice), (2R,6R)-HNK does not appear to inhibit the NMDAR.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [112]
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“(S)-ketamine has ~4-fold greater affinity/potency at inhibiting the NMDAR compared to its (R)-ketamine enantiomer 13, 111–115.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [112]
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“[3H]-MK-801 binding displacement studies showed that the affinity of (2R,6R)-HNK to displace MK-801 from the NMDAR is >100 μM, and that of (2S,6S)-HNK is 7–20 μM 111, 112.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [112]
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The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.
Wong, E. H. F., Kemp, J. A., Priestley, T., Knight, A. R., Woodruff, G. N., & Iversen, L. L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.18.7104 · Cited by 1,820
X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel
Nury, H., Van Renterghem, C., Weng, Y., Tran, A., Baaden, M., Dufresne, V., Changeux, J.-P., Sonner, J. M., Delarue, M., & Corringer, P.-J. (2011) · Nature · doi:10.1038/nature09647 · Cited by 412
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis
Mineur, Y. S., & Picciotto, M. R. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.004 · Cited by 285
Zarate, C. A., Brutsche, N., Laje, G., Luckenbaugh, D. A., Venkata, S. L. V., Ramamoorthy, A., Moaddel, R., & Wainer, I. W. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.03.004 · Cited by 282
Self-citationAnalysis of Mecamylamine Stereoisomers on Human Nicotinic Receptor Subtypes
Papke, R. L., Sanberg, P. R., & Shytle, R. D. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29581-1 · Cited by 271
Ebert, B., Mikkelsen, S. S., Thorkildsen, C., & Borgbjerg, F. M. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)01116-3 · Cited by 270
Xiao, Y., Meyer, E. L., Thompson, J. M., Surin, A. M., Wroblewski, J. T., & Kellar, K. J. (1998) · Molecular Pharmacology · doi:10.1124/mol.54.2.322 · Cited by 247
Self-citationPhilip, N. S., Carpenter, L. L., Tyrka, A. R., & Price, L. H. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1932-6 · Cited by 191
Ketamine: new uses for an old drug?
Hirota, K., & Lambert, D. G. (2011) · British Journal of Anaesthesia · doi:10.1093/bja/aer221 · Cited by 160
Yamakura, T., Chavez-Noriega, L. E., & Harris, R. A. (2000) · Anesthesiology · doi:10.1097/00000542-200004000-00033 · Cited by 141
Metabolism of Ketamine Stereoisomers by Human Liver Microsomes
Kharasch, E. D., & Labroo, R. B. (1992) · Anesthesiology · doi:10.1097/00000542-199212000-00022 · Cited by 140
Zhao, X., Venkata, S. L. V., Moaddel, R., Luckenbaugh, D. A., Brutsche, N. E., Ibrahim, L., Zarate Jr, C. A., Mager, D. E., & Wainer, I. W. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04198.x · Cited by 137
Self-citationLeung, L. Y., & Baillie, T. A. (1986) · Journal of Medicinal Chemistry · doi:10.1021/jm00161a043 · Cited by 135
Stereoselective and regiospecific hydroxylation of ketamine and norketamine
Desta, Z., Moaddel, R., Ogburn, E. T., Xu, C., Ramamoorthy, A., Venkata, S. L. V., Sanghvi, M., Goldberg, M. E., Torjman, M. C., & Wainer, I. W. (2012) · Xenobiotica · doi:10.3109/00498254.2012.685777 · Cited by 114
Self-citationCoates, K., & Flood, P. D. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704315 · Cited by 114
Moaddel, R., Venkata, S. L. V., Tanga, M. J., Bupp, J. E., Green, C. E., Iyer, L., Furimsky, A., Goldberg, M. E., Torjman, M. C., & Wainer, I. W. (2010) · Talanta · doi:10.1016/j.talanta.2010.08.005 · Cited by 108
Self-citationAdams, J. D., Jr., Baillie, T. A., Trevor, A. J., & Castagnoli, N. (1981) · Journal of Mass Spectrometry · doi:10.1002/bms.1200081103 · Cited by 105
Bolze, S., & Boulieu, R. (1998) · Clinical Chemistry · doi:10.1093/clinchem/44.3.560 · Cited by 71
Woolf, T. F., & Adams, J. D., Jr. (1987) · Xenobiotica · doi:10.3109/00498258709043993 · Cited by 65
Turfus, S. C., Parkin, M. C., Cowan, D., Halket, J. M., Smith, N. W., Braithwaite, R. A., Elliot, S. P., Steventon, G. B., & Kicman, A. T. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.026328 · Cited by 57
Moaddel, R., Jóźwiak, K., Yamaguchi, R., & Wainer, I. W. (2005) · Analytical Chemistry · doi:10.1021/ac0504464 · Cited by 40
Self-citationXiao, Y., Abdrakhmanova, G. R., Baydyuk, M., Hernandez, S. C., & Kellar, K. J. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.69 · Cited by 23
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NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., Alkondon, M., Yuan, P., Pribut, H. J., Singh, N. S., et al. (2016) · Nature · doi:10.1038/nature17998 · Cited by 1,609
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Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015198 · Cited by 1,260
Self-citationMechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127
R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine
Zhang, J.-C., Li, S.-X., & Hashimoto, K. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.11.033 · Cited by 357
Hashimoto, K. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12902 · Cited by 335
Metadata
- Authors
- Moaddel, R., Abdrakhmanova, G., Kozak, J., Jozwiak, K., Toll, L., Jimenez, L., Rosenberg, A., Tran, T., Xiao, Y., Zarate, C. A., & Wainer, I. W.
- Affiliations
- National Institutes of Health (US)
- Virginia Commonwealth University (US)
- Medical University of Lublin (PL)
- Torrey Pines Institute For Molecular Studies (US)
- SRI International (US)
- Georgetown University (US)
- Corresponding author
- Wainer, Irving W.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 698
- Issue
- 1-3
- Pages
- 228-234
- ISSN
- 0014-2999 (ISSN-L)
- PMC
- PMC3534778
- OpenAlex
- W2068032560
- Cited by
- 176
- References
- 22
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 14 · 2022: 14 · 2021: 15 · 2020: 23 · 2019: 11 · 2018: 15 · 2017: 16 · 2016: 15 · 2015: 14 · 2014: 9 · 2013: 4
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Intramural Research Programs of the National Institute of Aging (IWW)
- National Institute of Mental Health (CAZ)
- Brain & Behavior Research Foundation Bipolar Disorders Award (CAZ), NIA (N01AG-3–1009 (GA,LT,LJ))
- Foundation for Polish Science (FOCUS and TEAM Programmes) (KJ).
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- ketamine metabolites, norketamine, dehydronorketamine, hydroxynorketamine, alpha7 nicotinic acetylcholine receptor, α3β4 nicotinic acetylcholine receptor, negative allosteric modulation, NMDA receptor binding, nicotinic antagonists
- MeSH terms
- Acetylcholine, Anesthetics, Animals, Cell Line, Dose-Response Relationship, Drug, Ketamine, Receptors, Nicotinic, Receptors, N-Methyl-D-Aspartate, Nicotinic Agonists, Rats, Electrophysiological Phenomena, alpha7 Nicotinic Acetylcholine Receptor
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