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Fast acting antidepressant

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https://www.readbyqxmd.com/read/28916283/deuterated-d6-dextromethorphan-elicits-antidepressant-like-effects-in-mice
#1
Linda Nguyen, Anna L Scandinaro, Rae R Matsumoto
The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy...
September 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28735749/initiation-of-behavioral-response-to-antidepressants-by-cholecystokinin-neurons-of-the-dentate-gyrus
#2
Lucian Medrihan, Yotam Sagi, Zintis Inde, Oleh Krupa, Chelsea Daniels, Adrien Peyrache, Paul Greengard
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressant drugs, but the cellular and molecular mechanisms by which their therapeutic action is initiated are poorly understood. Here we show that serotonin 5-HT1B receptors in cholecystokinin (CCK) inhibitory interneurons of the mammalian dentate gyrus (DG) initiate the therapeutic response to antidepressants. In these neurons, 5-HT1B receptors are expressed presynaptically, and their activation inhibits GABA release. Inhibition of GABA release from CCK neurons disinhibits parvalbumin (PV) interneurons and, as a consequence, reduces the neuronal activity of the granule cells...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28731926/history-of-anaesthesia-the-ketamine-story-past-present-and-future
#3
Georges Mion
No abstract text is available yet for this article.
September 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28584860/integrative-analysis-of-sex-differences-in-the-rapid-antidepressant-effects-of-ketamine-in-preclinical-models-for-individualized-clinical-outcomes
#4
Samantha K Saland, Florian Duclot, Mohamed Kabbaj
In major depressive disorder, women exhibit higher lifetime prevalence and different antidepressant response rates than men, which illustrates the importance of examining individual differences in the pathophysiology of depression and therapeutic response. In recent years, the consideration of sex in related preclinical research has thus gained interest-particularly in light of novel evidence for rapid-acting antidepressants. Notably, the literature recently revealed a higher sensitivity of females to the antidepressant effects of the N-methyl-D-aspartate receptor antagonist ketamine, in both baseline and preclinical conditions...
April 2017: Current Opinion in Behavioral Sciences
https://www.readbyqxmd.com/read/28408831/modulation-of-the-activity-of-n-methyl-d-aspartate-receptors-as-a-novel-treatment-option-for-depression-current-clinical-evidence-and-therapeutic-potential-of-rapastinel-glyx-13
#5
REVIEW
Andrei-Nicolae Vasilescu, Nina Schweinfurth, Stefan Borgwardt, Peter Gass, Undine E Lang, Dragos Inta, Sarah Eckart
Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28357557/single-bolus-low-dose-of-ketamine-does-not-prevent-postpartum-depression-a-randomized-double-blind-placebo-controlled-prospective-clinical-trial
#6
Yang Xu, Yuantao Li, Xiaolei Huang, Daili Chen, Baozuan She, Daqing Ma
PURPOSE: Postpartum depression is a common complication of childbirth. In the last decade, it has been suggested that subdissociative-dose ketamine is a fast-acting antidepressant. We aimed to investigate the efficacy of low-dose ketamine administered during caesarean section in preventing postpartum depression. METHODS: Using a randomized, double-blind, placebo-controlled design, 330 parturients who were scheduled to undergo caesarean section were enrolled in this trial...
May 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28322281/identification-of-a-novel-fast-acting-gabaergic-antidepressant
#7
K M J McMurray, M J Ramaker, A M Barkley-Levenson, P S Sidhu, P K Elkin, M K Reddy, M L Guthrie, J M Cook, V H Rawal, L A Arnold, S C Dulawa, A A Palmer
Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST)...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28275719/a-negative-allosteric-modulator-for-%C3%AE-5-subunit-containing-gaba-receptors-exerts-a-rapid-and-persistent-antidepressant-like-action-without-the-side-effects-of-the-nmda-receptor-antagonist-ketamine-in-mice
#8
Panos Zanos, Mackenzie E Nelson, Jaclyn N Highland, Samuel R Krimmel, Polymnia Georgiou, Todd D Gould, Scott M Thompson
New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility. Ketamine promotes excitatory synaptic strength, likely by producing high-frequency correlated activity in mood-relevant regions of the forebrain. Negative allosteric modulators of GABA-A receptors containing α5 subunits (α5 GABA-NAMs) should also promote high-frequency correlated electroencephalogram (EEG) activity and should therefore exert rapid antidepressant responses...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28253930/rapid-and-stable-changes-in-maturation-related-phenotypes-of-the-adult-hippocampal-neurons-by-electroconvulsive-treatment
#9
Yuki Imoto, Eri Segi-Nishida, Hidenori Suzuki, Katsunori Kobayashi
Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression. Despite a long history of clinical use, its mechanism of action remains poorly understood. Recently, a novel cellular mechanism of antidepressant action has been proposed: the phenotype of mature brain neurons is transformed to immature-like one by antidepressant drug treatments. We show here that electroconvulsive stimulation (ECS), an animal model of ECT, causes profound changes in maturation-related phenotypes of neurons in the hippocampal dentate gyrus of adult mice...
March 2, 2017: Molecular Brain
https://www.readbyqxmd.com/read/27965425/essential-roles-of-ampa-receptor-glua1-phosphorylation-and-presynaptic-hcn-channels-in-fast-acting-antidepressant-responses-of-ketamine
#10
Ke Zhang, Ting Xu, Zhongmin Yuan, Zhisheng Wei, Vitor Nagai Yamaki, Mingfa Huang, Richard L Huganir, Xiang Cai
Although the molecular mechanism is not clear, the clinically tested drug ketamine has rapid antidepressant action that does not require the multiple weeks of treatment needed for other antidepressant drugs to have an effect. We showed that ketamine potentiated Schaffer collateral-CA1 cell excitatory synaptic transmission in hippocampal slice preparations from rodents and enhanced the phosphorylation of the GluA1 subunit on Ser(845) of the AMPA-type glutamate receptor in the hippocampal area CA1. These effects persisted when γ-aminobutyric acid (GABA) receptors were pharmacologically blocked...
December 13, 2016: Science Signaling
https://www.readbyqxmd.com/read/27960559/investigational-drugs-for-treating-major-depressive-disorder
#11
REVIEW
Ashish Dhir
Treatment of patients suffering from major depression could be highly challenging for psychiatrists. Intractability as well as relapse is commonly seen among these patients, leading to functional impairment and poor quality of life. The present review discusses some of the novel investigational drugs that are under pre-clinical or clinical phases in the treatment of major depression. Areas covered: Molecules belonging to different classes such as triple reuptake inhibitors, opioid receptors, ionotropic and metabotropic glutamate receptors, and neurotrophin in the treatment of major depression are covered in this article...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27878517/risks-associated-with-misuse-of-ketamine-as-a-rapid-acting-antidepressant
#12
REVIEW
Weili Zhu, Zengbo Ding, Yinan Zhang, Jie Shi, Kenji Hashimoto, Lin Lu
Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast-acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression...
December 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27870451/preclinical-sex-differences-in-depression-and-antidepressant-response-implications-for-clinical-research
#13
REVIEW
Nikolaos Kokras, Christina Dalla
Women suffer from depression and anxiety disorders more often than men, and as a result they receive antidepressants to a greater extent. Sex differences in antidepressant response in humans have been modestly studied, and results have been controversial. At the same time, preclinical studies on animal models of depression and antidepressant response have provided insights with regard to sex differences that could be useful for the design and interpretation of future clinical trials. This Mini-Review discusses such sex-differentiated findings with regard to the presentation of depression, endophenotypes, and antidepressant response...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27826228/potentiation-of-schaffer-collateral-ca1-synaptic-transmission-by-eef2k-and-p38-mapk-mediated-mechanisms
#14
Weiguang Weng, Ying Chen, Man Wang, Yinghan Zhuang, Thomas Behnisch
The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists. Even so, it remains open whether direct inhibition of eEF2K without altering up-stream or other signaling pathways affects hippocampal synaptic transmission and neuronal network synchrony. Inhibition of eEF2K by the selective and potent eEF2K inhibitor A-484954 induced a fast pre-synaptically mediated enhancement of synaptic transmission and synchronization of neural network activity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27806991/hippocampal-perineuronal-nets-are-required-for-the-sustained-antidepressant-effect-of-ketamine
#15
Jennifer J Donegan, Daniel J Lodge
Background: N-methyl-D-aspartate receptor antagonists, like ketamine, produce a rapid-acting and long-lasting antidepressant effect. Although the mechanism is not completely understood, ketamine is thought to preferentially target N-methyl-D-aspartate receptors on fast-spiking parvalbumin-containing interneurons. The function of parvalbumin-containing interneurons is dependent on perineuronal nets, a specialized form of extracellular matrix that surrounds these cells. Methods: Chondroitinase was used to enzymatically degrade perineuronal nets surrounding parvalbumin-containing interneurons in the ventral hippocampus, a region that is involved in the antidepressant response to ketamine...
April 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27785950/kinase-mediated-signaling-cascades-in-mood-disorders-and-antidepressant-treatment
#16
Li-Lian Yuan, Eric Wauson, Vanja Duric
Kinase-mediated signaling cascades regulate a number of different molecular mechanisms involved in cellular homeostasis, and are viewed as one of the most common intracellular processes that are robustly dysregulated in the pathophysiology of mood disorders such as depression. Newly emerged, rapid acting antidepressants are able to achieve therapeutic improvement, possibly in part, through stimulating activity of kinase-dependent signaling pathways. Thus, advancements in our understanding of how kinases may contribute to development and treatment of depression seem crucial...
September 2016: Journal of Neurogenetics
https://www.readbyqxmd.com/read/27784811/rapid-and-lasting-enhancement-of-dopaminergic-modulation-at-the-hippocampal-mossy-fiber-synapse-by-electroconvulsive-treatment
#17
Katsunori Kobayashi, Yuki Imoto, Fumi Yamamoto, Mayu Kawasaki, Miyuki Ueno, Eri Segi-Nishida, Hidenori Suzuki
Electroconvulsive therapy (ECT) is an established effective treatment for medication-resistant depression with the rapid onset of action. However, its cellular mechanism of action has not been revealed. We have previously shown that chronic antidepressant drug treatments enhance dopamine D1-like receptor-dependent synaptic potentiation at the hippocampal mossy fiber (MF)-CA3 excitatory synapse. In this study we show that ECT-like treatments in mice also have marked effects on the dopaminergic synaptic modulation...
January 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27743829/acute-agmatine-administration-similar-to-ketamine-reverses-depressive-like-behavior-induced-by-chronic-unpredictable-stress-in-mice
#18
Vivian B Neis, Luis E B Bettio, Morgana Moretti, Priscila B Rosa, Camille M Ribeiro, Andiara E Freitas, Filipe M Gonçalves, Rodrigo B Leal, Ana Lúcia S Rodrigues
Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants...
November 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27686025/lack-of-effect-of-chronic-ketamine-administration-on-depression-like-behavior-or-frontal-cortex-autophagy-in-female-and-male-icr-mice
#19
N Z Kara, G Agam, G W Anderson, N Zitron, H Einat
The acute antidepressant effects of ketamine provide hope for the development of a fast acting approach to treat depression but the consequences of chronic treatment with ketamine are still unclear. One theory regarding the acute effect is that ketamine acts through activation of mTOR but chronic activation of mTOR may lead to reduced autophagy and reduced autophagy could have negative consequences on neuronal plasticity and survival and on affect. To study the interaction between chronic ketamine administration, autophagy and depression the present study tested the effects of 3 weeks daily administration of 5 or 10mg/kg ketamine in both female and male ICR mice on behavior in the open field and the forced swim test and on frontal cortex levels of beclin-1 and p62, two proteins that serve as markers of autophagy...
September 26, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27634096/fast-acting-antidepressants-rapidly-stimulate-erk-signaling-and-bdnf-release-in-primary-neuronal-cultures
#20
Ashley E Lepack, Eunyoung Bang, Boyoung Lee, Jason M Dwyer, Ronald S Duman
Recent preclinical and clinical studies demonstrate that three functionally different compounds, the NMDA receptor channel blocker ketamine, mGlu2/3 receptor antagonist LY341495, and NMDA receptor glycine site agent GLYX-13 produce rapid and long lasting antidepressant effects. Furthermore, these agents are reported to stimulate ERK and mTORC1 signaling in brain. Here we used rat primary cortical culture neurons to further examine the cellular actions of these agents. The results demonstrate that low concentrations of all three compounds rapidly increase levels of the phosphorylated and activated forms of ERK and a downstream target of mTORC1, p70S6 kinase, in a concentration and time dependent manner...
December 2016: Neuropharmacology
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