This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Chen G, Mannens G, De Boeck M, Daly EJ, Canuso CM, Teuns G, et al. Comments to pharmacological and behavioral divergence of ketamine enantiomers by Jordi Bonaventura et al. Mol Psychiatry. 2022. In press.
Bonaventura J, Lam S, Carlton M, Boehm MA, Gomez JL, Solís O, et al. Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability. Mol Psychiatry. 2021. https://doi.org/10.1038/s41380-021-01093-2.
Hess EM, Riggs LM, Michaelides M, Gould TD. Mechanisms of ketamine and its metabolites as antidepressants. Biochem Pharmacol. 2022;197:114892.
Pacheco DDF, Romero TRL, Duarte IDG. Central antinociception induced by ketamine is mediated by endogenous opioids and μ- and δ-opioid receptors. Brain Res. 2014;1562:69–75.
Williams NR, Heifets BD, Blasey C, Sudheimer K, Pannu J, Pankow H, et al. Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry. 2018;175:1205–15.
Fava M, Stahl S, Pani L, De Martin S, Pappagallo M, Guidetti C, et al. REL-1017 (Esmethadone) as Adjunctive treatment in patients with major depressive disorder: a phase 2a randomized double-blind trial. Am J Psychiatry. 2022;179:122–31. https://doi.org/10.1176/appi.ajp.2021.21020197.
Codd EE, Shank RP, Schupsky JJ, Raffa RB. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995;274:1263–70.
Matsui A, Williams JT. Activation of µ-opioid receptors and block of KIR3 potassium channels and NMDA receptor conductance by l- and d-methadone in rat locus coeruleus. Br J Pharmacol. 2010;161:1403–13.
Gorman AL, Elliott KJ, Inturrisi CE. The d- and l- isomers of methadone bind to the non-competitive site on the N-methyl-d-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett. 1997;223:5–8.
Kenakin T, Christopoulos A. Analytical pharmacology: the impact of numbers on pharmacology. Trends Pharmacol Sci. 2011;32:189–96.
Zhang JC, Li SX, Hashimoto K. R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behav. 2014;116:137–41.
Zanos P, Highland JN, Liu X, Troppoli TA, Georgiou P, Lovett J, et al. (R)-Ketamine exerts antidepressant actions partly via conversion to (2R,6R)-hydroxynorketamine, while causing adverse effects at sub-anaesthetic doses. Br J Pharmacol. 2019;176:2573–92.
Shaffer CL, Osgood SM, Smith DL, Liu J, Trapa PE. Enhancing ketamine translational pharmacology via receptor occupancy normalization. Neuropharmacology. 2014;86:174–80.
De Luca MT, Badiani A. Ketamine self-administration in the rat: evidence for a critical role of setting. Psychopharmacology. 2011;214:549–56.
Geisslinger G, Hering W, Thomann P, Knoll R, Kamp HD, Brune K. Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. Br J Anaesth. 1993;70:666–71.
Portmann S, Kwan HY, Theurillat R, Schmitz A, Mevissen M, Thormann W. Enantioselective capillary electrophoresis for identification and characterization of human cytochrome P450 enzymes which metabolize ketamine and norketamine in vitro. J Chromatogr A. 2010;1217:7942–8.
Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1992;260:1209–13.
Vollenweider FX, Leenders KL, Øye I, Hell D, Angst J. Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET). Eur Neuropsychopharmacol. 1997;7:25–38.
Heifets BD, Bentzley BS, Williams N, Schatzberg AF. Unraveling the opioid actions of S-ketamine and R-ketamine: comment on Bonaventura et al. Mol Psychiatry. 2021;26:6104–6.
Leal GC, Bandeira ID, Correia-Melo FS, Telles M, Mello RP, Vieira F, et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci. 2021;271:577–82.
Takahashi N, Yamada A, Shiraishi A, Shimizu H, Goto R, Tominaga Y. Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study. BMC Psychiatry. 2021;21:1–13.
Sapkota A, Khurshid H, Qureshi IA, Jahan N, Went TR, Sultan W, et al. Efficacy and safety of intranasal esketamine in treatment-resistant depression in adults: a systematic review. Cureus. 2021;13:e17352.
Wilkinson ST, Toprak M, Turner MS, Levine SP, Katz RB, Sanacora G. Letters to the editor. Am J Psychiatry. 2017;174:695–6.
Passie T, Adams HA, Logemann F, Brandt SD, Wiese B, Karst M. Comparative effects of (S)-ketamine and racemic (R/S)-ketamine on psychopathology, state of consciousness and neurocognitive performance in healthy volunteers. Eur Neuropsychopharmacol. 2021;44:92–104.
Hashimoto K. Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochem Pharmacol. 2020;177:113935.
Brady JV. Animal models for assessing drugs of abuse. Neurosci Biobehav Rev. 1991;15:35–43.
Schatzberg AF. A word to the wise about ketamine. Am J Psychiatry. 2014;171:262–4.
Schatzberg AF. A word to the wise about intranasal esketamine. Am J Psychiatry. 2019;176:422–4.
Author information
Authors and Affiliations
Contributions
JB, YS, CJZ, and MM wrote the paper with input from all coauthors. All authors critically reviewed the content and approved the final version before submission. This work was supported by the NIDA Intramural Research Program (ZIA000069), and by Grants RYC-2019-027371-I (JB) and PID2020-117989RA-I00 (JB) funded by MCIN/AEI /10.13039/501100011033 and by “ESF Investing in your future”. .
Corresponding authors
Ethics declarations
Competing interests
CAZ is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation. CAZ is listed as co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereo-isomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and posttraumatic stress disorders. He has assigned his patent rights to the US government but will share a percentage of any royalties that may be received by the government. PJM and CJT are coinventors on patents regarding the use and methods of production for (2R,6R)-hydroxynorketamine. They have assigned their patent rights to the US government but will share a percentage of any royalties that may be received by the government. MM has received research funding from AstraZeneca, Redpin Therapeutics, and Attune Neurosciences. All other authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bonaventura, J., Lam, S., Carlton, M. et al. Time will tell. Reply to “Comments to pharmacological and behavioral divergence of ketamine enantiomers by Jordi Bonaventura et al.” by Chen et al.. Mol Psychiatry 27, 1863–1865 (2022). https://doi.org/10.1038/s41380-022-01480-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41380-022-01480-3