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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Editorial

Ketamine Metabolites-waiting in the Wings as Therapeutic Candidate for Depression?

Author(s): Ming Tatt Lee and Yu-Cheng Ho*

Volume 17, 2024

Published on: 04 September, 2023

Article ID: e080823219541 Pages: 2

DOI: 10.2174/1874467217666230808162402

open_access

[1]
Marwaha, S.; Palmer, E.; Suppes, T.; Cons, E.; Young, A.H.; Upthegrove, R. Novel and emerging treatments for major depression. Lancet, 2023, 401(10371), 141-153.
[http://dx.doi.org/10.1016/S0140-6736(22)02080-3] [PMID: 36535295]
[2]
Daly, E.J.; Singh, J.B.; Fedgchin, M.; Cooper, K.; Lim, P.; Shelton, R.C.; Thase, M.E.; Winokur, A.; Van Nueten, L.; Manji, H.; Drevets, W.C. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression. JAMA Psychiatry, 2018, 75(2), 139-148.
[http://dx.doi.org/10.1001/jamapsychiatry.2017.3739] [PMID: 29282469]
[3]
Daly, E.J.; Trivedi, M.H.; Janik, A.; Li, H.; Zhang, Y.; Li, X.; Lane, R.; Lim, P.; Duca, A.R.; Hough, D.; Thase, M.E.; Zajecka, J.; Winokur, A.; Divacka, I.; Fagiolini, A.; Cubala, W.J.; Bitter, I.; Blier, P.; Shelton, R.C.; Molero, P.; Manji, H.; Drevets, W.C.; Singh, J.B. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression. JAMA Psychiatry, 2019, 76(9), 893-903.
[http://dx.doi.org/10.1001/jamapsychiatry.2019.1189] [PMID: 31166571]
[4]
Johnston, J.N.; Henter, I.D.; Zarate, C.A., Jr The antidepressant actions of ketamine and its enantiomers. Pharmacol. Ther., 2023, 246, 108431.
[http://dx.doi.org/10.1016/j.pharmthera.2023.108431] [PMID: 37146727]
[5]
Zanos, P.; Moaddel, R.; Morris, P.J.; Georgiou, P.; Fischell, J.; Elmer, G.I.; Alkondon, M.; Yuan, P.; Pribut, H.J.; Singh, N.S.; Dossou, K.S.S.; Fang, Y.; Huang, X.P.; Mayo, C.L.; Wainer, I.W.; Albuquerque, E.X.; Thompson, S.M.; Thomas, C.J.; Zarate, C.A., Jr; Gould, T.D. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature, 2016, 533(7604), 481-486.
[http://dx.doi.org/10.1038/nature17998] [PMID: 27144355]
[6]
Li, Y.; Du, Y.; Wang, C.; Lu, G.; Sun, H.; Kong, Y.; Wang, W.; Lian, B.; Li, C.; Wang, L.; Zhang, X.; Sun, L. (2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models. Neurobiol. Stress, 2022, 21, 100503.
[http://dx.doi.org/10.1016/j.ynstr.2022.100503] [PMID: 36532380]
[7]
Ye, L.; Xiao, X.; Xu, Y.; Zheng, C.; Chen, S.; Luo, T.; Li, Z.; Du, Y.; Yuan, Y.; Li, L.; Liu, B.; Qin, W.; Chou, D. Prelimbic cortex miR-34a contributes to (2R,6R)-hydroxynorketamine-mediated antidepressant-relevant actions. Neuropharmacology, 2022, 208, 108984.
[http://dx.doi.org/10.1016/j.neuropharm.2022.108984] [PMID: 35131296]
[8]
Peng, W.H.; Kan, H.W.; Ho, Y.C. Periaqueductal gray is required for controlling chronic stress-induced depression-like behavior. Biochem. Biophys. Res. Commun., 2022, 593, 28-34.
[http://dx.doi.org/10.1016/j.bbrc.2022.01.025] [PMID: 35051779]
[9]
Xiong, Z.; Fujita, Y.; Zhang, K.; Pu, Y.; Chang, L.; Ma, M.; Chen, J.; Hashimoto, K. Beneficial effects of (R)-ketamine, but not its metabolite (2R,6R)-hydroxynorketamine, in the depression-like phenotype, inflammatory bone markers, and bone mineral density in a chronic social defeat stress model. Behav. Brain Res., 2019, 368, 111904.
[http://dx.doi.org/10.1016/j.bbr.2019.111904] [PMID: 30980851]
[10]
Yamaguchi, J.; Toki, H.; Qu, Y.; Yang, C.; Koike, H.; Hashimoto, K.; Mizuno-Yasuhira, A.; Chaki, S. (2R,6R)-Hydroxynorketamine is not essential for the antidepressant actions of (R)-ketamine in mice. Int. J. Neuropsychopharmacol., 2018, 43(9), 1900-1907.
[http://dx.doi.org/10.1038/s41386-018-0084-y] [PMID: 29802366]
[11]
Zhang, K.; Fujita, Y.; Hashimoto, K. Lack of metabolism in (R)-ketamine’s antidepressant actions in a chronic social defeat stress model. Sci. Rep., 2018, 8(1), 4007.
[http://dx.doi.org/10.1038/s41598-018-22449-9] [PMID: 29507385]
[12]
Chou, D. Brain-derived neurotrophic factor in the ventrolateral periaqueductal gray contributes to (2R,6R)-hydroxynorketamine-mediated actions. Int. J. Neuropharmacol., 2020, 170, 108068.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108068] [PMID: 32222405]

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