Arketamine for cognitive impairment in psychiatric disorders

Hashimoto, Kenji

doi:10.1007/s00406-023-01570-5

Cited by 24 publications

(10 citation statements)

References 155 publications

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“…This beneficial effect of (R)-ketamine could be blocked by ANA-12 pretreatment, a TrkB inhibitor, which suggests that this effect is possibly exerted via the activation of the BDNF-TrkB signaling, as well. Based on this, (R)-ketamine has been suggested as a potential therapeutic drug for disorders with cognitive impairment [ 7 , 17 ]. Theta rhythm has been shown to have a crucial role in cognitive processes (learning and memory) and in the control of complex behaviors [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats

Pothorszki,

Koncz,

Török

et al. 2024

Pharmaceuticals

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Differences in the pharmacological effects of (S)-ketamine and (R)-ketamine are at the focus of research. Clinical data and our rat studies confirmed the antidepressant effect of (S)- but not (R)-ketamine, with similar differences in quantitative electroencephalogram (EEG) and sleep effects. In contrast, studies mainly on mice showed some stronger, preferable effects of (R)-ketamine. EEG theta (5–9 Hz) rhythm originates from the hippocampus, and its power is associated with cognitive functions, attention, and decreased anxiety. To find a brain parameter that is not associated with the antidepressant effect of drugs and may confirm potent in vivo effects of (R)-ketamine in rats, theta EEG power-inducing effects of the two enantiomers were measured and compared for 23 h. EEG-equipped Wistar rats were treated with (R)-ketamine (7.5, 15, 30 mg/kg i.p.), (S)-ketamine (7.5 and 15 mg/kg i.p.), or vehicle at the beginning of the passive phase. Frontoparietal EEG, electromyogram, and motor activity were recorded. (R)-ketamine but not (S)-ketamine dose-dependently increased EEG theta power during wakefulness and rapid eye movement (REM) sleep for 23 h. These results suggest that (R)-ketamine has an effect on a hippocampal function that was not affected by (S)-ketamine and may be associated with neural plasticity and memory encoding.

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Section: Discussionmentioning

confidence: 99%

Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats

Pothorszki,

Koncz,

Török

et al. 2024

Pharmaceuticals

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“…The research indicates that ( R,S )-ketamine has enhance cognitive functions in patients with MDD. 20 , 21 Zhang et al 5 observed spatial working memory deficits in CCI mice lasting at least 21 days. In contrast, our study found that repeated doses of ( S )-ketamine (10 mg/kg/day for 5 days), unlike a single dose, effectively reversed spatial working memory impairment in CCI mice.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the normalization of gut microbial composition is believed to play a role in the therapeutic effects of several drugs. 20 , 47–49 For example, alterations in gut microbiota may contribute to the antidepressant-like effect of ( S )-norketamine, a major metabolite of ( S )-ketamine, in an inflammatory model of depression. 50 In our current study, ( S )-ketamine restored the composition of the gut microbiota in CCI mice.…”

Section: Discussionmentioning

confidence: 99%

Repeated ( S )-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota–brain axis

Jiang,

Wang,

Chen

et al. 2024

Gut Microbes

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Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic ( S )-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of ( S )-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated ( S )-ketamine treatments improved the abnormal composition of the gut microbiome (β-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut – brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with ( S )-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated ( S )-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated ( S )-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota – brain axis, primarily through the enhancement of hippocampal BDNF – TrkB signaling by butyrate.

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“…Therefore, synthesizing the above studies we can easily find that ( R )-ketamine has a weak inhibitory effect on cognition, may improve cognitive dysfunction caused by other causes (such as psychiatric disorders) to a certain extent ( Hashimoto, 2023 ), and may play a positive role in preventing or delaying the disease progression of AD, and it is expected to be a potential medication for preventing and treating cognitive deficits in patients in the future.…”

Section: Research On Non-depressive Conditionsmentioning

confidence: 99%

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications

Zhang,

Pu,

Liu

et al. 2024

Front. Pharmacol.

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(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson’s disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.

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Arketamine for cognitive impairment in psychiatric disorders

Cited by 24 publications

References 155 publications

Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats

Unique Effects of (R)-Ketamine Compared to (S)-Ketamine on EEG Theta Power in Rats

Repeated ( S )-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota–brain axis

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications

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