The International Journal of Neuropsychopharmacology
August 28, 2019
Jiancheng Zhang, Youge Qu, Lijia Chang et al.
56 citations
BACKGROUND: A recent study demonstrated that spine formation rates by ketamine in the prefrontal cortex (PFC) were not altered at 3-6 h following a single injection, but were markedly altered at 12-24 h. Here, we investigated the acute (3 h post-treatment) effects of (R)-ketamine in the decreased spine density in the medial PFC (mPFC) and hippocampus in susceptible mice after chronic social...
Behavioural Brain Research
August 1, 2019
Zhongwei Xiong, Yuko Fujita, Kai Zhang et al.
Inflammatory bone markers may play a role in the antidepressant actions of (R)-ketamine in susceptible mice after chronic social defeat stress (CSDS). In this study, we compared the effects of (R)-ketamine and its final metabolite (2R,6R)-hydroxynorketamine (HNK) in depression-like phenotypes, inflammatory bone markers and bone mineral density (BMD) in CSDS susceptible mice. We measured plasma...
The International Journal of Neuropsychopharmacology
July 16, 2019
Yukio Ago, Wataru Tanabe, Momoko Higuchi et al.
91 citations
BACKGROUND: Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism of ketamine enantiomers and their metabolites is not fully understood. In view of the involvement of mechanisms other than the N-methyl-D-aspartate receptor in ketamine's action, we investigated the effects of (R)-ketamine, (S)-ketamine, (R)-norketamine...
Psychiatry and Clinical Neurosciences
June 19, 2019
Kenji Hashimoto
325 citations
Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists...
Pharmacology, Biochemistry and Behavior
June 1, 2019
Lijia Chang, Kai Zhang, Yaoyu Pu et al.
174 citations
The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine produces rapid and sustained antidepressant effects in treatment-resistant patients with depression although intranasal use of (R,S)-ketamine in ketamine abusers is popular. In March 5, 2019, nasal spray of (S)-ketamine for treatment-resistant depression was approved as a new antidepressant by the US Food Drug Administration....
Pharmacology, Biochemistry and Behavior
2019
Nian-nian Huang, Dongyu Hua, Gaofeng Zhan et al.
ABSTRACT Ketamine, an N‐methyl‐d‐aspartic acid receptor (NMDAR) antagonist, elicits rapid‐acting and sustained antidepressant effects in treatment‐resistant depressed patients. Accumulating evidence suggests that gut microbiota via the gut‐brain axis play a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. Here we investigated the...
Expert Review of Neurotherapeutics
December 4, 2018
Kai Zhang, Kenji Hashimoto
133 citations
Introduction: Depression is one of the most disabling diseases worldwide. Approximately one-third of depressed patients are treatment-resistant to the currently available antidepressants and there is a significant therapeutic time lag of weeks to months. There is a clear unmet need for rapid-acting and more efficacious treatments. (R,S)-ketamine, an old anesthetic drug, appears now to be going...
European Archives of Psychiatry and Clinical Neuroscience
July 14, 2018
Kenji Hashimoto, Chun Yang
The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)ketamine has been hailed as the most important advance in the treatment of depression for the past 50 years. The rapid and sustained antidepressant effects of (R,S)-ketamine have spurred a great deal of research interest, with growing off-label use for the treatment of depression, although the concerns about the safety of repeated...
Biological Psychiatry
2018
Chun Yang, Q. Ren, Y. Qu et al.
249 citations
BACKGROUND The role of the mechanistic target of rapamycin (mTOR) signaling in the antidepressant effects of ketamine is controversial. In addition to mTOR, extracellular signal-regulated kinase (ERK) is a key signaling molecule in prominent pathways that regulate protein synthesis. (R)-Ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here we...
Translational Psychiatry
December 15, 2017
Chun Yang, Youge Qu, Yuko Fujita et al.
231 citations
Accumulating evidence suggests that the gut microbiota-brain axis plays a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. (R)-ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here, we investigated whether the gut microbiota plays a role in the antidepressant effects of these two ketamine...
The International Journal of Neuropsychopharmacology
November 14, 2017
Yukihiko Shirayama, Kenji Hashimoto
113 citations
Background: (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the...
Scientific Reports
November 10, 2017
Youge Qu, Chun Yang, Qian Ren et al.
126 citations
Accumulating evidence suggests a key role of the gut-microbiota-brain axis in the antidepressant actions of certain compounds. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, showed rapid and sustained antidepressant effects in treatment-resistant depressed patients. In contrast, another NMDAR antagonist, lanicemine, did not exhibit antidepressant effects in such patients....
Scientific Reports
June 5, 2017
Ze-Min Xie, Xingming Wang, Ning Xu et al.
69 citations
Although pain is frequently accompanied with depression, little is known about the risk factors contributing to individual differences to the comorbidity of pain and depression. In this study, we examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the individual differences in the development of neuropathic pain-induced depression. Rats were randomly...
The International Journal of Neuropsychopharmacology
October 7, 2016
Chao Dong, Ji-Chun Zhang, Wei Yao et al.
116 citations
Background: Similar to the N-methyl-D-aspartate receptor antagonist ketamine, the metabotropic glutamate 2/3 receptor antagonist, MGS0039, shows antidepressant effects. However, there are no reports comparing these 2 compounds in the social defeat stress model of depression. Methods: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible...
Expert Opinion on Therapeutic Targets
September 20, 2016
Kenji Hashimoto
68 citations
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants since this drug causes rapid-onset and sustained antidepressant effects in treatment resistant patients with depression. There are unanswered questions about how ketamine induces its rapid and sustained antidepressant actions. This key article suggests that (2R,6R)-HNK...
Psychopharmacology
August 3, 2016
Bangkun Yang, Ji-Chun Zhang, Mei Han et al.
93 citations
RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonists, including R-ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in animal models of depression. OBJECTIVE: We compared the rapid and sustained antidepressant effects of R-ketamine and rapastinel in the social defeat stress model. RESULTS: In the tail suspension and forced swimming tests, R-ketamine (10...
European Archives of Psychiatry and Clinical Neuroscience
April 18, 2016
Kenji Hashimoto, Takeharu Kakiuchi, Hiroyuki Ohba et al.
125 citations
R-ketamine appears to be a potent, long-lasting and safer antidepressant, relative to esketamine (S-ketamine), since it might be free of psychotomimetic side effects. Using [11C]raclopride and positron emission tomography (PET), we investigated whether esketamine and R-ketamine can affect dopamine D2/3 receptor binding in the conscious monkey brain. A single infusion of esketamine (0.5 mg/kg),...
Translational Psychiatry
February 23, 2016
H-L Sun, Z-Q Zhou, G.-F. Zhang et al.
87 citations
Although ketamine shows a rapid and sustained antidepressant effect, the precise mechanisms underlying its effect are unknown. Recent studies indicate a key role of p11 (also known as S100A10) in depression-like behavior in rodents. The present study aimed to investigate the role of p11 in the antidepressant-like action of ketamine in chronic unpredictable mild stress (CUMS) rat model. The...
Translational Psychiatry
September 1, 2015
Chun Yang, Yukihiko Shirayama, J-C Zhang et al.
600 citations
Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential...
Current Molecular Medicine
May 4, 2015
Yuta Ohgi, Takashi Futamura, Kenji Hashimoto
109 citations
Glutamate, a major excitatory neurotransmitter, plays important roles in synaptic plasticity, such as long-term potentiation (LTP) and new synapse formation. Growing evidence suggests that glutamate signaling is involved in the neurobiology of psychiatric disorders, including schizophrenia, major depressive disorder (MDD) and bipolar disorder (BP). Postmortem brain studies demonstrated altered...
Clinical Psychopharmacology and Neuroscience
April 1, 2015
Chun Yang, Kenji Hashimoto
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Combination of Nitrous Oxide with Isoflurane or Scopolamine for Treatment-resistant Major...
PLoS One
February 4, 2013
Xiancang Ma, Yonghui Dang, Min Jia et al.
115 citations
BACKGROUND: Clinical studies demonstrate that the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that...
Progress in neuro-psychopharmacology & biological psychiatry
August 15, 2011
Kenji Hashimoto
Major depressive disorder (MDD) is a common, chronic, recurrent mental illness that affects millions of individuals worldwide. Currently available antidepressants are known to affect the monoaminergic (e.g., serotonin, norepinephrine, and dopamine) systems in the brain. Accumulating evidence suggests that the glutamatergic neurotransmission via the excitatory amino acid glutamate also plays an...
Progress in Neuro-psychopharmacology and Biological Psychiatry
July 30, 2006
Eiji Shimizu, Hiroyuki Watanabe, Takashi Kojima et al.
103 citations
Although preclinical studies suggest that methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propan-1-one) and 5-MeO-MIPT (5-methoxy-N-methyl,N-isopropyl tryptamine) may have psychostimulant properties, the scientific reports about the clinical effects of these agents are scant. We describe a 27-year-old male patient with substance intoxication after a single ingestion of the mixture of...
Neuropharmacology
July 1990
Kenji Hashimoto, Tsuyoshi Goromaru
The effects of 3,4-methylenedioxymethamphetamine (MDMA) on the in vivo binding of [3H]paroxetine, a potent and selective 5-hydroxytryptamine (5-HT; serotonin) uptake inhibitor, in the brain of the mouse were studied. The distribution of radioactivity in the brain of the mouse, after intravenous administration of [3H]paroxetine, was significantly altered by pretreatment with MDMA (15 mg/kg,...