R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

Translational Psychiatry
C YangK Hashimoto

Abstract

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF-TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomoti...Continue Reading

References

Oct 1, 1991·The American Journal of Psychiatry·D C Javitt, S R Zukin
Feb 1, 1997·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·F X VollenweiderJ Angst
Feb 25, 2000·Biological Psychiatry·R M BermanJ H Krystal
Apr 5, 2002·Neuron·Eric J NestlerLisa M Monteggia
May 18, 2004·Brain Research. Brain Research Reviews·Kenji HashimotoMasaomi Iyo
Mar 29, 2006·Biological Psychiatry·Eric J Nestler, William A Carlezon
Apr 25, 2006·Biological Psychiatry·Ronald S Duman, Lisa M Monteggia
Aug 9, 2006·Archives of General Psychiatry·Carlos A ZarateHusseini K Manji
Jun 2, 2009·Brain Research Reviews·Kenji Hashimoto
Aug 4, 2010·Archives of General Psychiatry·Nancy DiazgranadosCarlos A Zarate
Aug 10, 2010·Anesthesiology·Edward F Domino
Apr 21, 2011·The Journal of Clinical Investigation·Maxime CazorlaDidier Rognan
Jul 23, 2011·Addiction·Celia J A MorganUNKNOWN Independent Scientific Committee on Drugs
Jul 30, 2011·Nature Protocols·Sam A GoldenScott J Russo
Oct 6, 2011·Pharmacology, Biochemistry, and Behavior·Rodrigo Machado-VieiraCarlos A Zarate
Jan 21, 2012·Pharmacology, Biochemistry, and Behavior·Yuko FujitaKenji Hashimoto
Oct 9, 2012·Science·Ronald S Duman, George K Aghajanian
Mar 5, 2013·European Archives of Psychiatry and Clinical Neuroscience·Kenji HashimotoAndrea Schmitt
Jun 4, 2013·Biological Psychiatry·John H KrystalRonald S Duman
Dec 10, 2013·Pharmacology, Biochemistry, and Behavior·Ji-Chun ZhangKenji Hashimoto
Mar 29, 2014·Psychopharmacology·Chun Yang, Kenji Hashimoto
May 23, 2014·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Kenji Hashimoto
Jul 21, 2014·Psychopharmacology·Guillaume FondLaurent Boyer
Dec 30, 2014·The International Journal of Neuropsychopharmacology·Ashley E LepackRonald S Duman
Jan 7, 2015·Current Opinion in Neurobiology·Lisa M Monteggia, Carlos Zarate
Jan 9, 2015·The International Journal of Neuropsychopharmacology·Chun YangKenji Hashimoto

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Citations

Feb 24, 2016·European Archives of Psychiatry and Clinical Neuroscience·Kenji Hashimoto
Mar 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Qian RenKenji Hashimoto
Oct 30, 2015·Acta Neuropsychiatrica·Kenji HashimotoMasaomi Iyo
Aug 3, 2016·European Archives of Psychiatry and Clinical Neuroscience·Yukihiko Shirayama, Kenji Hashimoto
Jul 14, 2016·Expert Opinion on Drug Discovery·Agnieszka Pałucha-Poniewiera, Andrzej Pilc
Sep 10, 2016·The International Journal of Neuropsychopharmacology·Bangkun YangKenji Hashimoto
Sep 21, 2016·Expert Opinion on Therapeutic Targets·Kenji Hashimoto
Nov 8, 2016·Biological Psychiatry·Panos ZanosTodd D Gould
Nov 12, 2016·The Journal of Nutritional Biochemistry·Ji-Chun ZhangKenji Hashimoto
Dec 15, 2016·Expert Opinion on Investigational Drugs·Ashish Dhir
Jan 18, 2017·International Journal of Psychiatry in Clinical Practice·Christoph KrausSiegfried Kasper
Jun 10, 2017·Expert Review of Neurotherapeutics·Gopalkumar RakeshPrakash S Masand
Mar 14, 2018·Molecular Psychiatry·P Zanos, T D Gould
Mar 9, 2018·CNS Drugs·Panos ZanosTodd D Gould
Jun 30, 2016·Therapeutic Advances in Psychopharmacology·John MullerSrinivas Pentyala
May 23, 2018·Medicinal Research Reviews·Xu-Feng Huang, Xueqin Song
Sep 22, 2016·Journal of Psychopharmacology·Christopher J Fitzpatrick, Jonathan D Morrow
Jun 13, 2018·The International Journal of Neuropsychopharmacology·Lijia ChangKenji Hashimoto
Dec 5, 2018·Expert Review of Neurotherapeutics·Kai Zhang, Kenji Hashimoto
Oct 10, 2018·Annual Review of Pharmacology and Toxicology·Todd D GouldScott M Thompson
Nov 18, 2018·The International Journal of Neuropsychopharmacology·Bashkim KadriuCarlos A Zarate
Mar 25, 2019·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Xi FangAilin Luo

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Methods Mentioned

BETA
pharmacotherapy

Software Mentioned

SPSS Statistics
PASW Statistics

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