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Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants
Open accessAbstract
For decades, symptoms of depression have been treated primarily with medications that directly target the monoaminergic brain systems, which typically take weeks to exert measurable effects and months to exert remission of symptoms. Low, subanesthetic doses of ( R,S)-ketamine (ketamine) result in the rapid improvement of core depressive symptoms, including mood, anhedonia, and suicidal ideation, occurring within hours following a single administration, with relief from symptoms typically lasting up to a week. The discovery of these actions of ketamine has resulted in a reconceptualization of how depression could be more effectively treated in the future. In this review, we discuss clinical data pertaining to ketamine and other rapid-acting antidepressant drugs, as well as the current state of pharmacological knowledge regarding their mechanism of action. Additionally, we discuss the neurobiological circuits that are engaged by this drug class and that may be targeted by a future generation of medications, for example, hydroxynorketamine; metabotropic glutamate receptor 2/3 antagonists; and N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and γ-aminobutyric acid receptor modulators.
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“Given that the evidence of PCP, MK-801, and memantine exerting antidepressant-like effects in rodents is mixed, with clinical studies either failing or lacking”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Gould et al., 2019
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“It appears that increased strength of excitatory neurotransmission, in particular involving AMPARs, represents a common downstream target that is necessary for antidepressant efficacy among classical and rapid-acting antidepressants (Alt et al., 2006; Gould et al., 2019; Thompson et al., 2015).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Gould et al., 2019
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“NMDAR antagonism may not fully explain the antidepressant effects of ketamine”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Gould et al., 2019
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“Preclinical studies suggest that the beneficial actions of ketamine are mediated by activation of both BDNF-TrkB signaling and endogenous synaptic strengthening mechanisms [114].”
From Beyond the serotonin deficit hypothesis: Communicating a neuroplasticity framework of major depressive disorder (2024) · cites this paper as [114]
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“Scopolamine administered to rodents also increases mTORC1 signaling, synaptogenesis, and antidepressant behavioral responses that are mTORC1 activation–dependent (115) and that have been functionally linked to disinhibition of somatostatin interneurons in the medial prefrontal cortex, a result that converges with the…”
BackgroundZarate, C. A., Mathews, D., Ibrahim, L., Chaves, J. F., Marquardt, C., Ukoh, I., Jolkovsky, L., Brutsche, N. E., Smith, M. A., & Luckenbaugh, D. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.019 · Cited by 255 · cited 2×
“However, the response rate was low and was not as robust or sustained as that typically observed with ketamine (42).”
BackgroundResultSelf-citationLateral habenula in the pathophysiology of depression
Yang, Y., Wang, H., Hu, J., & Hu, H. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.024 · Cited by 254 · cited 1×
“A fourth, more recent, putative NMDARdependent mechanism proposes ketamine inhibition of NMDAR-dependent high-frequency burst firing of a specific neuronal population in the lateral habenula, which will result in a decreased activity of negative valence brain circuits that are proposed to be abnormally enhanced in dep…”
BackgroundAntidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine
Fukumoto, K., Toki, H., Iijima, M., Hashihayata, T., Yamaguchi, J.-I., Hashimoto, K., & Chaki, S. (2017) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.239228 · Cited by 252
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“Indeed, there is extensive evidence that numerous growth-promoting signaling pathways are activated by ketamine and other rapid-acting antidepressants (72, 122, 123, 131).”
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“More recent controlled studies observed antidepressant actions of intravenous scopolamine 3–5 days following a single treatment (53, 54).”
BackgroundA role for AMPA receptors in mood disorders
Alt, A., Nisenbaum, E. S., Bleakman, D., & Witkin, J. M. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.12.022 · Cited by 238
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“Another placebo-controlled study of repeated adjunctive AZD6765 infusions administered daily over three weeks to subjects with treatment-resistant MDD found that AZD6765 (given at doses of either 100 mg or 150 mg) had antidepressant effects without dissociative side effects but was not rapid acting, as measured at ear…”
BackgroundAntidepressant-like actions of an AMPA receptor potentiator (LY392098)
Li, X., Tizzano, J. P., Griffey, K., Clay, M., Lindstrom, T., & Skolnick, P. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(00)00194-5 · Cited by 225
Neural correlates of change in major depressive disorder anhedonia following open-label ketamine
Lally, N., Nugent, A. C., Luckenbaugh, D. A., Niciu, M. J., Roiser, J. P., & Zarate, C. A. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114568041 · Cited by 224 · cited 1×
“Ketamine also rapidly improves anhedonia in depressed patients (29, 30).”
BackgroundSelf-citationAMPA Receptor Potentiators for the Treatment of CNS Disorders
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“No other treatment for depression—especially for TRD—has demonstrated comparable effects in terms of the magnitude of response following a single administration.”
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NMDA Receptors in the Central Nervous System
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“A functional NMDAR in brain cortical regions is most typically composed of two GluN1 (historically referred to as NR1) subunits and two GluN2 (historically referred to as NR2) subunits (60).”
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Iadarola, N. D., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Lundin, N. B., Nugent, A. C., Machado-Vieira, R., & Zarate, C. A. (2015) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622315579059 · Cited by 201 · cited 2×
“While ketamine’s antidepressant effects have been consistently replicated over the past decade (14), efforts to develop novel or more effective agents that mimic ketamine’s mechanism of action have proven difficult.”
BackgroundSelf-citationMiller, O. H., Moran, J. T., & Hall, B. J. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.028 · Cited by 200 · cited 1×
“A third hypothesis proposes a role for extrasynaptic NMDARs composed primarily of GluN2B that are tonically activated by ambient glutamate and, when inhibited, lead to activation of cellular plasticity cascades (75, 76).”
BackgroundThe role of eukaryotic elongation factor 2 kinase in rapid antidepressant action of ketamine
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“elongation factor 2 (eEF2)] that result in an increase in translation and release of BDNF and subsequent synaptic potentiation (73, 74).”
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“To date, the observed human clinical effects of GLYX-13 have been ambiguous and have yet to be fully reported, but they do suggest potential rapid and sustained antidepressant effects (49, 50).”
BackgroundSubunit-specific mechanisms and proton sensitivity of NMDA receptor channel block
Dravid, S. M., Erreger, K., Yuan, H., Nicholson, K., Le, P., Lyuboslavsky, P., Almonte, A., Murray, E., Mosley, C., Barber, J., et al. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.124958 · Cited by 184 · cited 1×
“However, other studies suggest no such selectivity (62, 63).”
BackgroundDifferent sensitivities of NMDA receptor channel subtypes to non-competitive antagonists
Yamakura, T., Mori, H., Hisashi, M., Shimoji, K., & Mishina, M. (1993) · Neuroreport · doi:10.1097/00001756-199306000-00021 · Cited by 181 · cited 1×
“However, other studies suggest no such selectivity (62, 63).”
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Self-citationEffects of a ketamine metabolite on synaptic NMDAR function
Suzuki, K., Nosyreva, E., Hunt, K. W., Kavalali, E. T., & Monteggia, L. M. (2017) · Nature · doi:10.1038/nature22084 · Cited by 180
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Convergent Mechanisms Underlying Rapid Antidepressant Action
Zanos, P., Thompson, S. M., Duman, R. S., Zarate, C. A., & Gould, T. D. (2018) · CNS Drugs · doi:10.1007/s40263-018-0492-x · Cited by 171
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mTOR activation is required for the antidepressant effects of mGluR2/3 blockade
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Ketamine: new uses for an old drug?
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“Since the discovery of the rapid antidepressant actions of ketamine, most studies assessing ketamine’s antidepressant effects have been designed, conducted, and analyzed using a commonly accepted view that ketamine and, possibly, norketamine are the active agents with clinical effects that are due to inhibition of the…”
BackgroundKoike, H., & Chaki, S. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.05.065 · Cited by 157
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Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials
Ballard, E. D., Wills, K. E., Lally, N., Richards, E. M., Luckenbaugh, D. A., Walls, T. L., Ameli, R., Niciu, M. J., Brutsché, N. E., Park, L., et al. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.04.057 · Cited by 155 · cited 1×
“The reduction in thoughts of suicide associated with ketamine treatment is correlated with the antianhedonic response, independent of depression improvement (31).”
BackgroundSelf-citationGABA interneurons mediate the rapid antidepressant-like effects of scopolamine
Wohleb, E. S., Wu, M., Gerhard, D. M., Taylor, S. R., Picciotto, M. R., Alreja, M., & Duman, R. S. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85033 · Cited by 144
Ketamine-induced anesthesia involves the N-methyl-d-aspartate receptor-channel complex in mice
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“This focus originates from anesthesia-focused experiments, where an early seminal study found that ketamine and norketamine exert anesthetic actions, but that the 6-HNKs do not, which parallels the potencies of ketamine, norketamine, and the 6-HNKs to inhibit the NMDAR (93, 94).”
BackgroundMoskal, J. R., Burch, R. M., Burgdorf, J. S., Kroes, R. A., Stanton, P. K., Disterhoft, J. F., & Leander, J. D. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.852536 · Cited by 133 · cited 2×
“To date, the observed human clinical effects of GLYX-13 have been ambiguous and have yet to be fully reported, but they do suggest potential rapid and sustained antidepressant effects (49, 50).”
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Pham, T. H., Defaix, C., Xu, X., Deng, S.-X., Fabresse, N., Alvarez, J.-C., Landry, D. W., Brachman, R. A., Denny, C. A., & Gardier, A. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.020 · Cited by 131
NMDAR-independent, cAMP-dependent antidepressant actions of ketamine
Wray, N. H., Schappi, J. M., Singh, H., Senese, N. B., & Rasenick, M. M. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0083-8 · Cited by 129
A Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders
Wilkinson, S. T., Toprak, M., Turner, M. S., Levine, S. P., Katz, R. B., & Sanacora, G. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17020239 · Cited by 125 · cited 1×
“These data have led to ketamine’s off-label use and the emergence of specialized ketamine clinics and emergency room protocols to treat severely depressed and suicidal individuals (32).”
BackgroundFischell, J., Van Dyke, A. M., Kvarta, M. D., LeGates, T. A., & Thompson, S. M. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.112 · Cited by 122
Self-citationSignaling networks in the pathophysiology and treatment of mood disorders
Gould, T. D., & Manji, H. K. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00426-9 · Cited by 120
Self-citationSanacora, G., Johnson, M. R., Khan, A., Atkinson, S. D., Riesenberg, R. R., Schronen, J. P., Burke, M. A., Zajecka, J. M., Barra, L., Su, H.-L., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.224 · Cited by 120 · cited 1×
“However, a larger 12-week course, adjunctive, repeateddose study of AZD6765 (50 mg or 150 mg) found that this agent did not separate from placebo (44).”
BackgroundDong, C., Zhang, J.-C., Yao, W., Ren, Q., Ma, M., Yang, C., Chaki, S., & Hashimoto, K. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw089 · Cited by 120
Navarria, A., Wohleb, E. S., Voleti, B., Ota, K. T., Dutheil, S., Lepack, A. E., Dwyer, J. M., Fuchikami, M., Becker, A., Drago, F., et al. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.06.012 · Cited by 118 · cited 1×
“Antagonists of M1 and M2 receptors have also produced an antidepressant and antianhedonic effect in animal models, similar to the actions of scopolamine (113, 114).”
ResultYao, N., Skiteva, O., Zhang, X., Svenningsson, P., & Chergui, K. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.239 · Cited by 118
Paul, R. K., Singh, N. S., Khadeer, M., Moaddel, R., Sanghvi, M., Green, C. E., O’Loughlin, K., Torjman, M. C., Bernier, M., & Wainer, I. W. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000285 · Cited by 115
Can, A., Zanos, P., Moaddel, R., Kang, H. J., Dossou, K. S. S., Wainer, I. W., Cheer, J. F., Frost, D. O., Huang, X.-P., & Gould, T. D. (2016) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.235838 · Cited by 115 · cited 1×
“However, ketamine has relatively low affinity for the majority of these targets, and in most cases, subanesthetic doses of ketamine are not expected to reach the brain levels necessary for effective interactions (37, 89, 90).”
BackgroundSelf-citationZanos, P., Piantadosi, S. C., Wu, H., Pribut, H. J., Dell, M. J., Can, A., Snodgrass, H. R., Zarate, C. A., Schwarcz, R. M., & Gould, T. D. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.225664 · Cited by 114 · cited 1×
“The NMDAR glycine site antagonist brainpenetrant prodrug 4-chlorokynurenine has been shown to exert antidepressant activity in preclinical models and is in human phase II clinical trials with results not yet reported (88).”
BackgroundSelf-citationLingford-Hughes, A. R., Hume, S. P., Feeney, A., Hirani, E., Osman, S., Cunningham, V. J., Pike, V. W., Brooks, D. J., & Nutt, D. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200207000-00013 · Cited by 112
Ghosal, S., Bang, E., Yue, W., Hare, B. D., Lepack, A. E., Girgenti, M. J., & Duman, R. S. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.06.017 · Cited by 111
Defining the role of NMDA receptors in anesthesia: Are we there yet?
Petrenko, A. B., Yamakura, T., Sakimura, K., & Baba, H. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.11.039 · Cited by 107 · cited 1×
“However, there is evidence that other targets contribute to anesthetic actions (65), such as ketamine blockade of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel (66).”
BackgroundZanos, P., Nelson, M. E., Highland, J. N., Krimmel, S. R., Georgiou, P., Gould, T. D., & Thompson, S. M. (2017) · eNeuro · doi:10.1523/eneuro.0285-16.2017 · Cited by 106
Self-citationLiu, R.-J., Duman, C., Kato, T., Hare, B., Lopresto, D., Bang, E., Burgdorf, J., Moskal, J., Taylor, J., Aghajanian, G., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.202 · Cited by 105 · cited 1×
“Upregulation of AMPAR synaptic expression has been measured in immunoblots from animals within 24 hours after treatment with ketamine and other putative rapid-acting antidepressant drugs (68, 71, 107, 129, 139).”
BackgroundChou, D., Peng, H.-Y., Lin, T.-B., Lai, C.-Y., Hsieh, M.-C., Wen, Y.-C., Lee, A.-S., Wang, H.-H., Yang, P.-S., Chen, G.-D., et al. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.06.033 · Cited by 104 · cited 1×
“The (2R,6R)-HNK metabolite [formed exclusively from (R)-ketamine] exerts rapid and sustained ketamine-like behavioral and cellular actions in vivo (68, 95, 96).”
BackgroundFukumoto, K., Iijima, M., & Chaki, S. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3378-0 · Cited by 102
Witkin, J. M., Overshiner, C. D., Li, X., Catlow, J. T., Wishart, G. N., Schober, D. A., Heinz, B. A., Nikolayev, A., Tolstikov, V., Anderson, W. H., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.216804 · Cited by 101 · cited 2×
“Antagonists of M1 and M2 receptors have also produced an antidepressant and antianhedonic effect in animal models, similar to the actions of scopolamine (113, 114).”
MethodResultGu, G., Lorrain, D. S., Wei, H., Cole, R. L., Zhang, X., Daggett, L. P., Schaffhauser, H., Bristow, L. J., & Lechner, S. M. (2008) · Brain Research · doi:10.1016/j.brainres.2007.12.057 · Cited by 99
Glutamatergic Modulators in Depression
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Self-citationAMPA Receptor Potentiators: Application for Depression and Parkinsons Disease
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“Past treatment approaches (such as total sleep deprivation and ECT) and emerging findings with other medications, including scopolamine, (S)-ketamine, and GLYX-13, support the notion that depression can be treated rapidly, provided that the correct receptors, synapses, and/or circuits are targeted.”
BackgroundInfluentialBDNF Release and Signaling Are Required for the Antidepressant Actions of GLYX-13
Kato, T., Fogaça, M. V., Deyama, S., Li, X.-Y., Fukumoto, K., & Duman, R. S. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.220 · Cited by 88 · cited 1×
“Deletion of forebrain BDNF or TrkB and prevention of TrkB activation hinder the actions of rapid-acting antidepressant compounds in preclinical models (74, 110, 131, 132, 135).”
BackgroundOral Scopolamine Augmentation in Moderate to Severe Major Depressive Disorder
Khajavi, D., Farokhnia, M., Modabbernia, A., Ashrafi, M., Abbasi, S.-H., Tabrizi, M. H., & Akhondzadeh, S. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12m07706 · Cited by 86 · cited 1×
“It was subsequently reported that oral, twice-daily scopolamine had a small but superior antidepressant effect, compared to placebo, within 4 days of treatment initiation (55).”
BackgroundSynthesis and N-Methyl-d-aspartate (NMDA) Receptor Activity of Ketamine Metabolites
Morris, P. J., Moaddel, R., Zanos, P., Moore, C. E., Gould, T., Zarate, C. A., & Thomas, C. J. (2017) · Organic Letters · doi:10.1021/acs.orglett.7b02177 · Cited by 83
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“Historically, ECT, when efficacious, has a faster onset than monoamine-targeting antidepressants (8).”
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Jiménez-Sánchez, L., Campa, L., Auberson, Y. P., & Adell, A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.123 · Cited by 80
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“An early study found that intramuscular administration of scopolamine resulted in an antidepressant effect following the second of three administrations (52).”
BackgroundPozzi, L., Dorocic, I. P., Wang, X., Carlén, M., & Meletis, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083879 · Cited by 74
mGlu2/3 Receptor Antagonists as Novel Antidepressants
Chaki, S. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.03.008 · Cited by 73
Atack, J. R., Maubach, K. A., Wafford, K. A., O'Connor, D. V., Rodrigues, A. D., Evans, D. C., Tattersall, F. D., Chambers, M. S., MacLeod, A. M., Eng, W., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.157636 · Cited by 72
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Rapid Acting Antidepressants in Chronic Stress Models: Molecular and Cellular Mechanisms
Hare, B. D., Ghosal, S., & Duman, R. S. (2017) · Chronic Stress · doi:10.1177/2470547017697317 · Cited by 67
Kiselycznyk, C., Jury, N. J., Halladay, L. R., Nakazawa, K., Mishina, M., Sprengel, R., Grant, S. G. N., Svenningsson, P., & Holmes, A. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.03.023 · Cited by 58
Enhancing ketamine translational pharmacology via receptor occupancy normalization
Shaffer, C. L., Osgood, S. M., Smith, D. L., Liu, J., & Trapa, P. E. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.07.008 · Cited by 55 · cited 1×
“However, ketamine has relatively low affinity for the majority of these targets, and in most cases, subanesthetic doses of ketamine are not expected to reach the brain levels necessary for effective interactions (37, 89, 90).”
BackgroundEfficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain
Kroin, J. S., Das, V., Moric, M. M., & Buvanendran, A. (2019) · Regional Anesthesia & Pain Medicine · doi:10.1136/rapm-2018-000013 · Cited by 49 · cited 1×
“Additional studies have identified biological effects of (2R,6R)-HNK relevant to depression (98, 101–105) as well as effectiveness of (2R,6R)-HNK in ameliorating chronic pain symptoms in mice (106).”
BackgroundRajagopal, L., Burgdorf, J. S., Moskal, J. R., & Meltzer, H. Y. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.10.060 · Cited by 45 · cited 1×
“Furthermore, GLYX-13 administered at antidepressant-relevant doses prevented the NMDAR inhibition–mediated cognitive side effects of ketamine (112).”
BackgroundIntracellular Signaling Pathways Involved in ( S )- and ( R )-Ketamine Antidepressant Actions
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Metadata
- Authors
- Gould, T. D., Zarate, C. A., & Thompson, S. M.
- Affiliations
- University of Maryland, Baltimore (US)
- National Institutes of Health (US)
- Corresponding author
- Gould, Todd D.
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2019-01-06
- Volume
- 59
- Issue
- 1
- Pages
- 213-236
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- PMC
- PMC6364552
- OpenAlex
- W2897395578
- Cited by
- 133
- References
- 163
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 16 · 2023: 21 · 2022: 17 · 2021: 22 · 2020: 24 · 2019: 12
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH086828, R01MH107615, ZIAMH002857)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- rapid-acting antidepressants, ketamine, depression, mechanism of action, hydroxynorketamine, NMDA receptor modulators, anhedonia, suicidal ideation
- MeSH terms
- Animals, Antidepressive Agents, Brain, Depression, Humans, Ketamine
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