Ketamine is a racemic mixture of the enantiomers R-ketamine and S-ketamine (esketamine). S-ketamine has greater analgesic and anesthetic effects than R-ketamine and is less likely to cause psychotomimetic and other adverse effects. There is therefore an emerging interest favoring the use of S-ketamine over racemic ketamine when the drug is used for analgesia or anesthesia. This article examines...
Abstract Objective This research was aimed to evaluate the behaviors of short‐ or long‐term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Background Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity...
Ketamine, a molecule of many faces, has contributed immeasurably to numerous realms of clinical practice and scientific inquiry. From anesthesia and analgesia to depression and schizophrenia, it continues to shed light on the molecular underpinnings of pain, consciousness, and the pathophysiology of neuropsychiatric disorders. In particular, research on ketamine's mechanism of action is...
X-ray powder diffraction data, unit-cell parameters, and space group for S -2-(methylamino)-2-phenylcyclohexan-1-one hydrochloride, C 13 H 18 ClNO, are reported [ a = 6.578 (1) Å, b = 13.250 (2) Å, c = 15.096 (2) Å, β = 91.619 (3)°, unit-cell volume V = 1315(1) Å 3 , Z = 4, and space group P 2 1 ]. All measured lines were indexed and are consistent with the P 2 1 space group. No detectable...
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 glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (KET) produces rapid and sustained antidepressant effects in patients. Tiletamine (TIL; 2-ethylamino-2-thiophen-2-yl-cyclohexan-1-one) is another uncompetitive NMDA receptor antagonist, used in a medical (veterinary) setting as an anesthetic tranquilizer. Here, we compared the behavioral actions of KET and TIL in a variety...
Background: Targeting the N-methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with...
The molecular mechanisms underlying major depressive disorder remain poorly understood, and current antidepressant treatments have many shortcomings. The recent discovery that a single intravenous infusion of ketamine at a subanesthetic dose had robust, rapid and sustained antidepressant effects in individuals with treatment-resistant depression inspired tremendous interest in investigating the...
To study the clinical effect of a single ketamine infusion, 0.5 mg/kg body weight, in bipolar depressive patients receiving mood-stabilising drugs, not improving on antidepressants. Previously, in such patients, we had found a correlation between clinical efficacy, serum brain-derived neurotrophic factor and vitamin B12 levels and a rapid improvement in neurocognitive performance. The study...
Based on the discovery of the robust antidepressant effects of ketamine in patients with depression, including those with treatment-resistant depression, agents acting on the glutamatergic system have drawn much attention as potential novel antidepressants. Among the agents acting on the glutamatergic system, preclinical data have indicated that the group II metabotropic glutamate (mGlu)...
BACKGROUND: This study evaluated efficacy and safety of intravenous subanesthetic doses of esketamine using an administration time of 10 minutes in patients with treatment-resistant depression and bipolar depression. METHODS: , Fourth Edition, Text Revision criteria, and these patients received rapid infusion of esketamine between June 2012 and December 2015. The Montgomery-Åsberg Depression...
Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known...
PLoS OneMay 4, 2017Marion Rame, D. Caudal, E. Schenker et al.
Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be...
To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored. Sixteen participants with bipolar depression and a Scale for Suicidal Ideation (SSI) score of ≥4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg). Current pharmacotherapy was...
Summary Background The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine. Methods In this multicentre, randomised,...
Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients...
A combination of antidepressant drugs and psychotherapy exhibits more promising efficacy in treating fear disorders than either treatment alone, but underlying mechanisms of such treatments remain largely unknown. Here we investigated the role of DNA methylation of the brain-derived neurotrophic factor (Bdnf) gene in the therapeutic effects of ketamine in combination with extinction training in...
Abstract What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of...
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers...
We present a review and analysis of the ethical considerations in off-label ketamine use for severe, treatment-resistant depression. The analysis of ethical considerations is contextualised in an overview of the evidence for ketamine use in depression, and a review of the drug's safety profile. We find that, based on current evidence, ketamine use for severe, treatment-resistant depression does...