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Mechanisms of the Antidepressant Effects of Ketamine Enantiomers and Their Metabolites

  • Soichiro Ide
    Affiliations
    Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
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  • Kazutaka Ikeda
    Correspondence
    Address correspondence to Kazutaka Ikeda, Ph.D., Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
    Affiliations
    Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Search for articles by this author
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      References

        • Krystal J.H.
        • Sanacora G.
        • Duman R.S.
        Rapid-acting glutamatergic antidepressants: The path to ketamine and beyond.
        Biol Psychiatry. 2013; 73: 1133-1141
        • Yang C.
        • Shirayama Y.
        • Zhang J.C.
        • Ren Q.
        • Yao W.
        • Ma M.
        • et al.
        R-ketamine: A rapid-onset and sustained antidepressant without psychotomimetic side effects.
        Transl Psychiatry. 2015; 5: e632
        • Zanos P.
        • Moaddel R.
        • Morris P.J.
        • Georgiou P.
        • Fischell J.
        • Elmer G.I.
        • et al.
        NMDAR inhibition-independent antidepressant actions of ketamine metabolites.
        Nature. 2016; 533: 481-486
        • Zhang J.C.
        • Li S.X.
        • Hashimoto K.
        R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine.
        Pharmacol Biochem Behav. 2014; 116: 137-141
        • Yang C.
        • Ren Q.
        • Qu Y.
        • Zhang J.C.
        • Ma M.
        • Dong C.
        • et al.
        Mechanistic target of rapamycin-independent antidepressant effects of (R)-ketamine in a social defeat stress model.
        Biol Psychiatry. 2018; 83: 18-28
        • Yang C.
        • Kobayashi S.
        • Nakao K.
        • Dong C.
        • Han M.
        • Qu Y.
        • et al.
        AMPA receptor activation–independent antidepressant actions of ketamine metabolite (S)-norketamine.
        Biol Psychiatry. 2018; 84: 591-600
        • Suzuki K.
        • Nosyreva E.
        • Hunt K.W.
        • Kavalali E.T.
        • Monteggia L.M.
        Effects of a ketamine metabolite on synaptic NMDAR function.
        Nature. 2017; 546: E1-E3
        • Shirayama Y.
        • Hashimoto K.
        Lack of antidepressant effects of (2R,6R)-hydroxynorketamine in a rat learned helplessness model: Comparison with (R)-ketamine.
        Int J Neuropsychopharmacol. 2018; 21: 84-88
        • Yamamoto T.
        • Nakayama T.
        • Yamaguchi J.
        • Matsuzawa M.
        • Mishina M.
        • Ikeda K.
        • et al.
        Role of the NMDA receptor GluN2D subunit in the expression of ketamine-induced behavioral sensitization and region-specific activation of neuronal nitric oxide synthase.
        Neurosci Lett. 2016; 610: 48-53
        • Ide S.
        • Ikekubo Y.
        • Mishina M.
        • Hashimoto K.
        • Ikeda K.
        Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine.
        J Pharmacol Sci. 2017; 135: 138-140

      Linked Article

      • AMPA Receptor Activation–Independent Antidepressant Actions of Ketamine Metabolite (S)-Norketamine
        Biological PsychiatryVol. 84Issue 8
        • Preview
          Ketamine, an N-methyl-D-aspartate receptor antagonist, exerts robust antidepressant effects in patients with treatment-resistant depression. The precise mechanisms underlying ketamine’s antidepressant actions remain unclear, although previous research suggests that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) activation plays a role. We investigated whether (S)-norketamine and (R)-norketamine, the two main metabolites of (R,S)-ketamine, also play a significant role in ketamine’s antidepressant effects and whether the effects are mediated by AMPAR.
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