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ketamine pharmacology

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https://www.readbyqxmd.com/read/28340572/does-sevoflurane-add-to-outpatient-procedural-sedation-in-children-a-randomised-clinical-trial
#1
Hugo Sérgio de Oliveira Gomes, Heloisa de Sousa Gomes, Joji Sado-Filho, Luciane Rezende Costa, Paulo Sucasas Costa
BACKGROUND: There is little evidence concerning the effect of sevoflurane in outpatient procedural sedation, especially in children. We hypothesised that the addition of sevoflurane to a sedation regimen improves children's behaviour with minimal adverse events. METHODS: This is a randomised, triple-blind clinical trial conducted on an outpatient basis. Participants were 27 healthy children aged 4 to 6 years, who previously refused dental treatment with non-pharmacologic methods...
March 24, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28339593/selective-pharmacological-augmentation-of-hippocampal-activity-produces-a-sustained-antidepressant-like-response-without-abuse-related-or-psychotomimetic-effects
#2
Flavia R Carreno, Gregory T Collins, Alan Frazer, Daniel J Lodge
Background: Selective augmentation of hippocampal activity in ways similar to that caused by ketamine may have therapeutic advantages over ketamine, which has psychotomimetic and reinforcing effects likely due to effects outside the hippocampus (i.e., off-target effects). Methods: Here we evaluated the antidepressant-like response to a negative allosteric modulator of α5 subunit- containing gamma aminobutyric acid subtype A receptors, L-655,708, as these receptors are expressed to a much greater extent in the hippocampus than in other brain areas...
January 25, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28294453/a-translational-approach-for-nmda-receptor-profiling-as-a-vulnerability-biomarker-for-depression-and-schizophrenia
#3
Handan Gunduz-Bruce, Joshua Kenney, Suravi Changlani, Aldo Peixoto, Ralitza Gueorguieva, Cheryl Leone, Nina Stachenfeld
Altered N-methyl-D-aspartate (NMDA) receptor activity and glutamate signaling may underlie the pathogenesis of both schizophrenia and depression in subgroups of patients. In schizophrenia, pharmacologic modeling, postmortem and imaging data suggest reduced NMDA signaling. In contrast, recent clinical trials demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed patients suggest increased NMDA receptor signaling. We conducted a proof of concept study to assess whether there is any in vivo evidence for an inverse association in depression and schizophrenia with respect to the NMDA receptor function...
March 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28285123/preclinical-predictors-that-the-orthosteric-mglu2-3-receptor-antagonist-ly3020371-will-not-engender-ketamine-associated-neurotoxic-motor-cognitive-subjective-or-abuse-liability-related-effects
#4
J M Witkin, J A Monn, J Li, B Johnson, D L McKinzie, X-S Wang, B A Heinz, R Li, P L Ornstein, S C Smith, C H Mitch, D O Calligaro, S Swanson, D Allen, K Phillips, G Gilmour
The novel mGlu2/3 receptor antagonist, LY3020371 has been shown to produce antidepressant-like effects comparable to that of the clinically-effective antidepressant ketamine. In the present study, we investigated whether LY3020371 would be predicted to be free of the side-effects and safety pharmacology issues associated with ketamine. In contrast to ketamine, LY3020371 produced small increases in locomotion and did not impair motor performance on an inverted. Ketamine, but not LY3020371, increased dopamine efflux in the nucleus accumbens of rats...
March 8, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28284817/differential-effects-of-gaseous-versus-injectable-anesthetics-on-changes-in-regional-cerebral-blood-flow-and-metabolism-induced-by-l-dopa-in-a-rat-model-of-parkinson-s-disease
#5
Zisis Bimpisidis, Carl M Öberg, Natallia Maslava, M Angela Cenci, Cornelia Lundblad
Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-2-deoxyglucose) with a highly sensitive autoradiographic method...
March 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28250331/elucidation-of-the-role-of-dorsal-raphe-serotonergic-neurons-in-mood-regulation-using-pharmacological-and-viral-vector-based-approaches
#6
Kazuki Nagayasu
 Growing evidence indicates that serotonergic neurons play a crucial role in brain function and dysfunction, such as in major depressive disorder. However, the complexity of serotonergic projections severely hampers the elucidation of their precise mechanisms. Here we summarize our recent studies on the effects of ketamine and olanzapine, which have been reported to be effective in treatment-resistant depression, on dorsal raphe nucleus serotonergic neurons, using microdialysis, electrophysiology experiments, and slice cultures...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28237716/clostridium-perfringens-epsilon-toxin-induces-permanent-neuronal-degeneration-and-behavioral-changes
#7
Winston E Morris, Jorge Goldstein, Leandro M Redondo, Adriana Cangelosi, Patricia Geoghegan, Marcela Brocco, Fabián C Loidl, Mariano E Fernandez-Miyakawa
Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice...
February 22, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28215996/morphological-and-behavioral-responses-of-zebrafish-after-24h-of-ketamine-embryonic-exposure
#8
Luís M Félix, Cindy Serafim, Maria J Martins, Ana M Valentim, Luís M Antunes, Manuela Matos, Ana M Coimbra
Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24h-LC50 was calculated from percent survival using probit analysis. Based on the 24h-LC50 (94.4mgL(-1)), embryos (2hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24h to ketamine concentrations of 50, 70 or 90mgL(-1)...
April 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28196426/development-of-a-functional-observational-battery-in-the-minipig-for-regulatory-neurotoxicity-assessments
#9
Miao Zhong, Catherine Shoemake, Amber Fuller, David White, Chris Hanks, Derek Brocksmith, Jason Liu, Shayne Gad, Guy Bouchard, Alain Stricker-Krongrad
A functional observational battery (FOB) is recommended as the first-tier neurotoxicity screening in the preclinical safety pharmacology testing guidelines. Minipigs have increasingly been used in regulatory toxicology studies; however, no current FOB protocol is available for neurotoxicity testing in these species. Hence, a minipig FOB instrument was developed. A complete crossover study with Sinclair minipigs was performed to evaluate physiologic, neurologic, and behavioral effects of amphetamine, ketamine, and diazepam...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28158165/ketamine-an-update-on-cellular-and-subcellular-mechanisms-with-implications-for-clinical-practice
#10
Gary J Iacobucci, Ognjen Visnjevac, Leili Pourafkari, Nader Djalal Nader
BACKGROUND: Ketamine is one of the oldest hypnotic agents used to provide an anesthetic agent with analgesic properties and minimal suppressive effects on respiration. The ability of ketamine in modulating glutamatergic (N-methyl D-aspartate) pain receptors has made this anesthetic drug a new option for the management of patients with chronic pain syndromes. Further preclinical and clinical findings suggest ketamine may have wide ranging effects on both cognition and development. Recent advances have revealed an unprecedented role for ketamine in the acute management of depression...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28125634/pacap-protects-adult-neural-stem-cells-from-the-neurotoxic-effect-of-ketamine-associated-with-decreased-apoptosis-er-stress-and-mtor-pathway-activation
#11
Shiva Mansouri, Ingrid Agartz, Sven-Ove Ögren, Cesare Patrone, Mathias Lundberg
Ketamine administration is a well-established approach to mimic experimentally some aspects of schizophrenia. Adult neurogenesis dysregulation is associated with psychiatric disorders, including schizophrenia. The potential role of neurogenesis in the ketamine-induced phenotype is largely unknown. Recent results from human genetic studies have shown the pituitary adenylate cyclase-activating polypeptide (PACAP) gene is a risk factor for schizophrenia. Its potential role on the regulation of neurogenesis in experimental model of schizophrenia remains to be investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28114089/-non-conventional-pharmacological-agents-for-the-treatment-of-bipolar-disorder-%C3%AE-systematic-review-of-the-evidence
#12
K N Fountoulakis, D Balaris, V Nikolaou, J Νimatoudis
Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options are also complex and often unsatisfactory. Typically the so-called "mood stabilizers" are used in the treatment of BD and in this class lithium and specific antiepileptics are included. The present study aimed to systematically review the literature concerning the presence of randomized double blind clinical trials of 'non conventional' pharmaceutical treatment options...
October 2016: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28111761/what-is-the-mechanism-of-ketamine-s-rapid-onset-antidepressant-effect-a-concise-overview-of-the-surprisingly-large-number-of-possibilities
#13
REVIEW
S E Strasburger, P M Bhimani, J H Kaabe, J T Krysiak, D L Nanchanatt, T N Nguyen, K A Pough, T A Prince, N S Ramsey, K H Savsani, L Scandlen, M J Cavaretta, R B Raffa
WHAT IS KNOWN AND OBJECTIVE: Abundant clinical data now confirm that ketamine produces a remarkable rapid-onset antidepressant effect - hours or days - in contrast to the delayed onset (typically weeks) of current antidepressant drugs. This surprising and revolutionary finding may lead to the development of life-saving pharmacotherapy for depressive illness by reducing the high suicide risk associated with the delayed onset of effect of current drugs. As ketamine has serious self-limiting drawbacks that restrict its widespread use for this purpose, a safer alternative is needed...
January 22, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28079589/in-vogue-ketamine-for-neuroprotection-in-acute-neurologic-injury
#14
Josh D Bell
Neurologic deterioration following acute injury to the central nervous system may be amenable to pharmacologic intervention, although, to date, no such therapy exists. Ketamine is an anesthetic and analgesic emerging as a novel therapy for a number of clinical entities in recent years, including refractory pain, depression, and drug-induced hyperalgesia due to newly discovered mechanisms of action and new application of its known pharmacodynamics. In this focused review, the evidence for ketamine as a neuroprotective agent in stroke, neurotrauma, subarachnoid hemorrhage, and status epilepticus is highlighted, with a focus on its applications for excitotoxicity, neuroinflammation, and neuronal hyperexcitability...
April 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28062203/semi-mechanistic-computer-simulation-of-psychotic-symptoms-in-schizophrenia-with-a-model-of-a-humanized-cortico-striatal-thalamocortical-loop
#15
Athan Spiros, Patrick Roberts, Hugo Geerts
Despite new insights into the pathophysiology of schizophrenia and clinical trials with highly selective drugs, no new therapeutic breakthroughs have been identified. We present a semi-mechanistic Quantitative Systems Pharmacology (QSP) computer model of a biophysically realistic cortical-striatal-thalamo-cortical loop. The model incorporates the direct, indirect and hyperdirect pathway of the basal ganglia and CNS drug targets that modulate neuronal firing, based on preclinical data about their localization and coupling to voltage-gated ion channels...
February 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28035869/comparative-efficacy-and-tolerability-of-pharmacological-and-somatic-interventions-in-adult-patients-with-treatment-resistant-depression-a-systematic-review-and-network-meta-analysis
#16
Katerina Papadimitropoulou, Carla Vossen, Andreas Karabis, Christina Donatti, Nicole Kubitz
OBJECTIVE: Major depressive disorder (MDD) affects about 10-15% of the general population in a lifetime. A considerable number of patients fail to achieve full symptom remission despite adequate treatment and are considered treatment resistant (TRD). The current study compared the relative efficacy and tolerability of pharmacological and somatic TRD interventions by means of a Bayesian network meta-analysis. RESEARCH DESIGN AND METHODS: An electronic literature search of MEDLINE, MEDLINE In-Process, EMBASE, PsycInfo, EconLit and Cochrane Library databases for trials published between September 2003 and September 2014 was conducted...
February 6, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28017918/effects-of-ketamine-administration-on-mtor-and-reticulum-stress-signaling-pathways-in-the-brain-after-the-infusion-of-rapamycin-into-prefrontal-cortex
#17
Helena M Abelaira, Gislaine Z Réus, Zuleide M Ignácio, Maria Augusta B Dos Santos, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Monique Michels, Mariane Abatti, Beatriz Sonai, Felipe Dal Pizzol, André F Carvalho, João Quevedo
Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC...
December 3, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27986606/imaging-the-neuroplastic-effects-of-ketamine-with-vbm-and-the-necessity-of-placebo-control
#18
A Höflich, S Ganger, M Tik, A Hahn, G S Kranz, T Vanicek, M Spies, C Kraus, C Windischberger, S Kasper, D Winkler, R Lanzenberger
In the last years a plethora of studies have investigated morphological changes induced by behavioural or pharmacological interventions using structural T1-weighted MRI and voxel-based morphometry (VBM). Ketamine is thought to exert its antidepressant action by restoring neuroplasticity. In order to test for acute impact of a single ketamine infusion on grey matter volume we performed a placebo-controlled, double-blind investigation in healthy volunteers using VBM. 28 healthy individuals underwent two MRI sessions within a timeframe of 2 weeks, each consisting of two structural T1-weighted MRIs within a single session, one before and one 45min after infusion of S-ketamine (bolus of 0...
February 15, 2017: NeuroImage
https://www.readbyqxmd.com/read/27968884/psychiatric-symptoms-in-individuals-who-use-ketamine-versus-methamphetamine-implications-for-glutamatergic-and-dopaminergic-model-for-schizophrenia-a-cohort-study
#19
Yanhui Liao, Chang Qi, Qiuxia Wu, Jinsong Tang
BACKGROUND: Both ketamine and methamphetamine have been used for studying the positive, negative, and cognitive symptoms, and dopaminergic and GABAergic dysfunction observed in acute schizophrenia. We aimed to explore and compare the prevalence and factor structure of psychotic symptoms in chronic ketamine and methamphetamine users. METHODS: We recruited chronic ketamine and methamphetamine users from the Guangzhou Baiyun and Kangda voluntary drug rehabilitation centres in the Hunan Province, China...
October 2016: Lancet
https://www.readbyqxmd.com/read/27965560/ketamine-50-years-of-modulating-the-mind
#20
REVIEW
Linda Li, Phillip E Vlisides
Ketamine was introduced into clinical practice in the 1960s and continues to be both clinically useful and scientifically fascinating. With considerably diverse molecular targets and neurophysiological properties, ketamine's effects on the central nervous system remain incompletely understood. Investigators have leveraged the unique characteristics of ketamine to explore the invariant, fundamental mechanisms of anesthetic action. Emerging evidence indicates that ketamine-mediated anesthesia may occur via disruption of corticocortical information transfer in a frontal-to-parietal ("top down") distribution...
2016: Frontiers in Human Neuroscience
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