Kim J, Farchione T, Potter A et al (2019) Esketamine for treatment-resistant depression—First FDA-approved antidepressant in a new class. N Engl J Med 381:1–4. https://doi.org/10.1056/nejmp1903305

Article  PubMed  Google Scholar 

Spravato (2019) | European Medicines Agency (EMA). https://www.ema.europa.eu/en/medicines/human/EPAR/spravato. Accessed 18 Aug 2024

SPRAVATO ® (cloridrato de escetamina) novo registo. In: Agência Nacional de Vigilância Sanitária - Anvisa. https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/spravato-r-cloridrato-de-escetamina-novo-registo. Accessed 18 Aug 2024

White PF, Ham J, Way WL, Trevor AJ (1980) Pharmacology of ketamine isomers in surgical patients. Anesthesiology 52:231–239

Article  CAS  PubMed  Google Scholar 

White PF, Schüttler J, Shafer A et al (1985) Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth 57:197–203. https://doi.org/10.1093/bja/57.2.197

Article  CAS  PubMed  Google Scholar 

Zhang JC, Li SX, Hashimoto K (2014) R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behav 116:137–141. https://doi.org/10.1016/j.pbb.2013.11.033

Article  CAS  PubMed  Google Scholar 

Chang L, Zhang K, Pu Y et al (2019) Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine. Pharmacol Biochem Behav 181:53–59. https://doi.org/10.1016/j.pbb.2019.04.008

Article  CAS  PubMed  Google Scholar 

Yang C, Shirayama Y, Zhang J et al (2015) R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry 5:e632. https://doi.org/10.1038/tp.2015.136

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang C, Han M, Zhang J-C et al (2016) Loss of parvalbumin-immunoreactivity in mouse brain regions after repeated intermittent administration of esketamine, but not R-ketamine. Psychiatry Res 239:281–283. https://doi.org/10.1016/j.psychres.2016.03.034

Article  CAS  PubMed  Google Scholar 

Zhang K, Yang C, Chang L et al (2020) Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1. Transl Psychiatry 10:32. https://doi.org/10.1038/s41398-020-0733-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fukumoto K, Toki H, Iijima M et al (2017) Antidepressant potential of (R)-ketamine in rodent models: comparison with (S)-ketamine. J Pharmacol Exp Ther 361:9–16. https://doi.org/10.1124/jpet.116.239228

Article  CAS  PubMed  Google Scholar 

Zanos P, Moaddel R, Morris PJ et al (2016) NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533:481–486. https://doi.org/10.1038/nature17998

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu J, Hawkins E, Phillips K, Deshpande LS (2020) Assessment of ketamine and its enantiomers in an Organophosphate-based rat model for features of Gulf War Illness. Int J Environ Res Public Health 17. https://doi.org/10.3390/ijerph17134710

Article  PubMed  PubMed Central  Google Scholar 

Rafało-Ulińska A, Pałucha-Poniewiera A (2022) The effectiveness of (R)-ketamine and its mechanism of action differ from those of (S)-ketamine in a chronic unpredictable mild stress model of depression in C57BL/6J mice. Behav Brain Res 418:113633. https://doi.org/10.1016/j.bbr.2021.113633

Article  CAS  PubMed  Google Scholar 

Zhao L, Zhang G, Lou X et al (2024) Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023. Eur Arch Psychiatry Clin Neurosci. https://doi.org/10.1007/s00406-024-01809-9. Eur Arch Psychiatry Clin Neurosci

Article  PubMed  Google Scholar 

He T, Wang D, Wu Z et al (2022) A bibliometric analysis of research on (R)-ketamine from 2002 to 2021. Neuropharmacology 218:109207. https://doi.org/10.1016/j.neuropharm.2022.109207

Article  CAS  PubMed  Google Scholar 

Baudot J, Soeiro T, Tambon M et al (2022) Safety concerns on the abuse potential of esketamine: multidimensional analysis of a new anti-depressive drug on the market. Fundam Clin Pharmacol 36:572–581. https://doi.org/10.1111/fcp.12745

Article  CAS  PubMed  Google Scholar 

Bonaventura J, Lam S, Carlton M et al (2021) Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability. Mol Psychiatry 26:6704–6722. https://doi.org/10.1038/s41380-021-01093-2

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hashimoto K (2023) Arketamine for cognitive impairment in psychiatric disorders. Eur Arch Psychiatry Clin Neurosci. https://doi.org/10.1007/s00406-023-01570-5

Article  PubMed  PubMed Central  Google Scholar 

Wang X, Chang L, Tan Y et al (2021) (R)-ketamine ameliorates the progression of experimental autoimmune encephalomyelitis in mice. Brain Res Bull 177:316–323. https://doi.org/10.1016/j.brainresbull.2021.10.013

Article  CAS  PubMed  Google Scholar 

Wang X, Chang L, Wan X et al (2022) (R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: a role of gut-microbiota-brain axis. Neurobiol Dis 165:105635. https://doi.org/10.1016/j.nbd.2022.105635

Article  CAS  PubMed  Google Scholar 

Wang X, Yang J, Hashimoto K (2022) (R)-ketamine as prophylactic and therapeutic drug for neurological disorders: beyond depression. Neurosci Biobehav Rev 139:104762. https://doi.org/10.1016/j.neubiorev.2022.104762

Article  CAS  PubMed  Google Scholar 

Fujita A, Fujita Y, Pu Y et al (2020) MPTP-induced dopaminergic neurotoxicity in mouse brain is attenuated after subsequent intranasal administration of (R)-ketamine: a role of TrkB signaling. Psychopharmacology 237:83–92. https://doi.org/10.1007/s00213-019-05346-5

Article  CAS  PubMed  Google Scholar 

Zhang S, Pu Y, Liu J et al (2024) Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications. Front Pharmacol 15:1337749. https://doi.org/10.3389/fphar.2024.1337749

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leal GC, Bandeira ID, Correia-Melo FS et al (2021) Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci 271:577–582. https://doi.org/10.1007/s00406-020-01110-5

Article  PubMed  Google Scholar 

Leal GC, Souza-Marques B, Mello RP et al (2023) Arketamine as adjunctive therapy for treatment-resistant depression: a placebo-controlled pilot study. J Affect Disord 330:7–15. https://doi.org/10.1016/j.jad.2023.02.151

Article  CAS  PubMed  Google Scholar 

Zhang J-C, Yao W, Hashimoto K (2022) Arketamine, a new rapid-acting antidepressant: a historical review and future directions. Neuropharmacology 218:109219. https://doi.org/10.1016/j.neuropharm.2022.109219

Article  CAS  PubMed  Google Scholar 

Wei Y, Chang L, Hashimoto K (2022) Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor. Mol Psychiatry 27:559–573. https://doi.org/10.1038/s41380-021-01121-1

Article  CAS  PubMed  Google Scholar 

Hashimoto K, Zhao M-M, Zhu T-T et al (2024) Ketamine and its two enantiomers in anesthesiology and psychiatry: a historical review and future directions. J Anesth Translational Med. https://doi.org/10.1016/j.jatmed.2024.07.001

Article  Google Scholar 

Tricco AC, Lillie E, Zarin W et al (2018) PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 169:467–473. https://doi.org/10.7326/M18-0850