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Fast acting antidepressant

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https://www.readbyqxmd.com/read/29763645/agmatine-potentiates-neuroprotective-effects-of-subthreshold-concentrations-of-ketamine-via-mtor-s6-kinase-signaling-pathway
#1
Mauren K Tavares, Suellen Dos Reis, Nicolle Platt, Isabella A Heinrich, Ingrid A V Wolin, Rodrigo B Leal, Manuella P Kaster, Ana Lúcia S Rodrigues, Andiara E Freitas
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most robust neurobiological findings in the pathophysiology of major depressive disorder (MDD) over the last 40 years. The persistent increase in glucocorticoids levels induces morphological and anatomical changes in the brain, especially in the hippocampus. Ketamine represents a major advance for the treatment of MDD, however the psychotomimetic effects of this compound limit its widespread use. Agmatine is a neuromodulator that has been shown to be a putative novel and well-tolerated antidepressant/augmenter drug...
May 12, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29718013/ketamine-for-treatment-resistant-depression-a-new-advocate
#2
Rodrigo Pérez-Esparza
Current alternatives for the treatment of major depressive disorder lack efficacy and have a delayed onset of action. Recently, the glutamatergic neurotransmission system has been noted to play an important role in the pathophysiology of this disorder. Ever since the first report of the antidepressant effects of the N-methyl-D-aspartate receptor antagonist, ketamine, research has been redirected to novel therapeutic targets. With this rapidly growing evidence of a fast-acting antidepressant such as ketamine, as well as its efficacy in treatment-resistant cases of depression, off-label use has become popular in certain settings...
2018: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/29691465/longitudinal-two-photon-imaging-in-somatosensory-cortex-of-behaving-mice-reveals-dendritic-spine-formation-enhancement-by-subchronic-administration-of-low-dose-ketamine
#3
Evgeny Pryazhnikov, Ekaterina Mugantseva, Plinio Casarotto, Julia Kolikova, Senem Merve Fred, Dmytro Toptunov, Ramil Afzalov, Pirta Hotulainen, Vootele Voikar, Ryan Terry-Lorenzo, Sharon Engel, Sergei Kirov, Eero Castren, Leonard Khiroug
Ketamine, a well-known anesthetic, has recently attracted renewed attention as a fast-acting antidepressant. A single dose of ketamine induces rapid synaptogenesis, which may underlie its antidepressant effect. To test whether repeated exposure to ketamine triggers sustained synaptogenesis, we administered a sub-anesthetic dose of ketamine (10 mg/kg i.p.) once-daily for 5 days, and repeatedly imaged dendritic spines of the YFP-expressing pyramidal neurons in somatosensory cortex of awake female mice using in vivo two-photon microscopy...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29664276/effects-of-n-n-dimethyltryptamine-dmt-on-rat-behaviors-relevant-to-anxiety-and-depression
#4
Lindsay P Cameron, Charlie J Benson, Lee E Dunlap, David E Olson
Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N,N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats...
April 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29525411/can-we-increase-the-speed-and-efficacy-of-antidepressant-treatments-part-ii-glutamatergic-and-rna-interference-strategies
#5
REVIEW
F Artigas, P Celada, A Bortolozzi
In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals...
April 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29478700/effective-use-of-animal-models-for-therapeutic-development-in-psychiatric-and-substance-use-disorders
#6
REVIEW
Anthony G Phillips, Mark A Geyer, Trevor W Robbins
Athina Markou and others argue forcefully for the adoption of a "translational-back translational strategy" for central nervous system drug discovery involving novel application of drugs with established safety profiles in proof-of-principle studies in humans, which in turn encourage parallel studies using experimental animals to provide vital data on the neural systems and neuropharmacological mechanisms related to the actions of the candidate drugs. Encouraged by the increasing adoption of drug-development strategies involving reciprocal information exchange between preclinical animal studies and related clinical research programs, this review presents additional compelling examples related to the following: 1) the treatment of cognitive deficits that define attention-deficit/hyperactivity disorder; 2) the development of fast-acting antidepressants based on promising clinical effects with low doses of the anesthetic ketamine; and 3) new and effective medications for the treatment of substance misuse...
January 31, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29395043/calcium-calmodulin-dependent-protein-kinase-ii-and-eukaryotic-elongation-factor-2-kinase-pathways-mediate-the-antidepressant-action-of-ketamine
#7
Chinnakkaruppan Adaikkan, Elham Taha, Iliana Barrera, Orit David, Kobi Rosenblum
BACKGROUND: Ketamine is an N-methyl-D-aspartate receptor antagonist, which on administration produces fast-acting antidepressant responses in patients with major depressive disorder. Yet, the mechanism underlying the antidepressant action of ketamine remains unclear. METHODS: To unravel the mechanism of action of ketamine, we treated wild-type C57BL/6 mice with calcium/calmodulin-dependent protein kinase II (CaMKII) specific inhibitor tatCN21 peptide. We also used eukaryotic elongation factor 2 kinase (eEF2K) (also known as CaMKIII) knockout mice...
December 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29228215/mitochondria-are-critical-for-bdnf-mediated-synaptic-and-vascular-plasticity-of-hippocampus-following-repeated-electroconvulsive-seizures
#8
Fenghua Chen, Maryam Ardalan, Betina Elfving, Gregers Wegener, Torsten M Madsen, Jens R Nyengaard
Background: Electroconvulsive therapy is a fast-acting and efficient treatment of depression used in the clinic. The underlying mechanism of its therapeutic effect is still unclear. However, recovery of synaptic connections and synaptic remodeling is thought to play a critical role for the clinical efficacy obtained from a rapid antidepressant response. Here, we investigated the relationship between synaptic changes and concomitant nonneuronal changes in microvasculature and mitochondria and its relationship to brain-derived neurotrophic factor level changes after repeated electroconvulsive seizures, an animal model of electroconvulsive therapy...
March 1, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29173709/new-insight-into-the-mechanisms-of-fast-acting-antidepressants-what-we-learn-from-scopolamine
#9
Christoph Anacker
No abstract text is available yet for this article.
January 1, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29137178/antidepressants-and-mood-stabilizers-novel-research-avenues-and-clinical-insights-for-bipolar-depression
#10
REVIEW
In Hee Shim, Young Sup Woo, Moon-Doo Kim, Won-Myong Bahk
The concept of the bipolar-spectrum and of mixed features being a bridge between major depressive disorders and bipolar disorders (BDs) has become increasingly important in mood-disorder diagnoses. Under these circumstances, antidepressants (ADs) and mood stabilizers (MSs) should be used with caution in the treatment of major depressive episodes (MDEs) and to obtain long-term stability in BDs. Before treating MDEs, screening tools, specific symptom evaluation and medical history should be used to distinguish between bipolarity and mixed features in patients for whom AD monotherapy may present a risk...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29042527/-biomarkers-for-mood-disorders-and-a-novel-antidepressant-r-ketamine
#11
Kenji Hashimoto
Depression is often misdiagnosed as major depressive disorder in patients with bipolar disorder. Therapeutic drugs for these two disorders are quite different, but the anesthetic ketamine shows fast-acting antidepressant effects in treatment-resistant patients with these disorders. Here, we discuss biomarkers for both disorders, recent findings regarding ketamine, and predictable biomarkers for ketamine's antidepressant actions.
October 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28916283/deuterated-d6-dextromethorphan-elicits-antidepressant-like-effects-in-mice
#12
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...
October 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28735749/initiation-of-behavioral-response-to-antidepressants-by-cholecystokinin-neurons-of-the-dentate-gyrus
#13
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
#14
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
#15
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
#16
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
#17
RANDOMIZED CONTROLLED TRIAL
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
#18
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)...
February 2018: 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
#19
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
#20
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
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