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ketamine pharmacology

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https://www.readbyqxmd.com/read/28196426/development-of-a-functional-observational-battery-in-the-minipig-for-regulatory-neurotoxicity-assessments
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
January 10, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27965425/essential-roles-of-ampa-receptor-glua1-phosphorylation-and-presynaptic-hcn-channels-in-fast-acting-antidepressant-responses-of-ketamine
#13
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/27903678/adnp-is-a-therapeutically-inducible-repressor-of-wnt-signaling-in-colorectal-cancer
#14
Cristina Blaj, Agnes Bringmann, Eva Marina Schmidt, Manuela Urbischek, Sebastian Lamprecht, Thomas Fröhlich, Georg J Arnold, Stefan Krebs, Helmut Blum, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
PURPOSE: Constitutively active WNT signaling is hallmark of colorectal cancers and driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer. EXPERIMENTAL DESIGN: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer, and cell biology approaches to determine its function...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27844474/assessment-of-acute-pain-in-trauma-a-retrospective-prehospital-evaluation
#15
Stine Hebsgaard, Anne Mannering, Stine T Zwisler
OBJECTIVE: To elucidate pain treatment with analgesics in a prehospital trauma population. DESIGN: Retrospective database study. SETTING: Prehospital data from the anesthesiologist-manned Mobile Emergency Care Unit (MECU) in Odense, Denmark, were extracted and subjected to analysis. PATIENTS: During the period of January 1, 2013 to December 31, 2014, patients with the diagnoses "unspecified multiple injuries," "examination and observation following traffic accident," "examination and observation following other accident," and "commotio cerebri" were included in the analysis...
September 2016: Journal of Opioid Management
https://www.readbyqxmd.com/read/27842942/evaluation-of-50-khz-ultrasonic-vocalizations-in-animal-models-of-mania-ketamine-and-lisdexamfetamine-induced-hyperlocomotion-in-rats
#16
Etieli Wendler, Camila Pasquini de Souza, Debora Dalla Vecchia, Luiz Kae Sales Kanazawa, Palloma de Almeida Soares Hocayen, Markus Wöhr, Rainer K W Schwarting, Roberto Andreatini
Drug-induced hyperlocomotion in rodents is frequently used as a behavioral model for mania. However, the use of locomotor activity as the single parameter in these animal models of mania may pose some limitations for developing new pharmacological treatments. Thus, alternative behavioral markers are required. Fifty-kHz ultrasonic vocalizations (USV), which are thought to represent positive affect, are increased by the administration of the psychostimulant d-amphetamine, an effect that can be prevented by lithium treatment, the gold standard antimanic drug for treating bipolar disorder...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27836553/how-much-alcohol-is-in-ketamine-s-antidepressant-action
#17
REVIEW
Udo Bonnet
Ketamine is approved to start and maintain anaesthesia or analgesia. Ketamine is also known to be neurotoxic and an old drug of abuse. Numerous studies have proven a rapid and strong antidepressant response (AR) following parenteral sub-anaesthetic ketamine doses when applied the first time to patients with treatment resistant unipolar or bipolar major depression. This rapid and robust AR is encouraging, though short-lived (usually up to seven days). There is growing evidence that repeated und escalating ketamine administrations exert longer-lasting AR than single infusions...
January 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27832755/experience-of-the-use-of-ketamine-to-manage-opioid-withdrawal-in-an-addicted-woman-a-case-report
#18
Laurence Lalanne, Chloe Nicot, Jean-Philippe Lang, Gilles Bertschy, Eric Salvat
BACKGROUND: Opioids are good painkillers, but many patients treated with opioids as painkillers developed a secondary addiction. These patients need to stop misusing opioids, but the mild-to-severe clinical symptoms associated with opioid withdrawal risk increasing their existing pain. In such cases, ketamine, which is used by anaesthetists and pain physicians to reduce opioid medication, may be an effective agent for managing opioid withdrawal. CASE PRESENTATION: We describe the case of a woman who developed a severe secondary addiction to opioids in the context of lombo-sciatic pain...
November 10, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27828892/exploring-opioid-sparing-multimodal-analgesia-options-in-trauma-a-nursing-perspective
#19
Denise Sullivan, Mary Lyons, Robert Montgomery, Ann Quinlan-Colwell
Challenges with opioids (e.g., adverse events, misuse and abuse with long-term administration) have led to a renewed emphasis on opioid-sparing multimodal management of trauma pain. To assess the extent to which currently available evidence supports the efficacy and safety of various nonopioid analgesics and techniques to manage trauma pain, a literature search of recently published references was performed. Additional citations were included on the basis of authors' knowledge of the literature. Effective options for opioid-sparing analgesics include oral and intravenous (IV) acetaminophen; nonsteroidal anti-inflammatory drugs available via multiple routes; and anticonvulsants, which are especially effective for neuropathic pain associated with trauma...
November 2016: Journal of Trauma Nursing: the Official Journal of the Society of Trauma Nurses
https://www.readbyqxmd.com/read/27798810/emergence-delirium-in-pediatric-anesthesia
#20
REVIEW
Arthura D Moore, Doralina L Anghelescu
Emergence delirium (ED) is a complex of perceptual disturbances and psychomotor agitation that occurs most commonly in preschool-aged children in the early postanesthetic period. The incidence of ED varies between 10 and 80% in children and is perceived as a troublesome clinical situation by 42% of pediatric anesthesiologists. Although these events are often short lived, they increase the risk of self-injury and delayed discharge, require additional nursing staff and can increase medical care costs, all of which are causes for concern...
February 2017: Paediatric Drugs
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