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ketamine pharmacology

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https://www.readbyqxmd.com/read/29151192/impact-of-oral-ketamine-augmentation-on-hospital-admissions-in-treatment-resistant-depression-and-ptsd-a-retrospective-study
#1
John Hartberg, Simone Garrett-Walcott, Angelo De Gioannis
RATIONALE: Depressive episodes are the leading cause of mental health-related hospital admissions in Australia, and 44% of those admitted have a previous history of hospitalisations for depression (Admitted patient mental health-related care: (Australian Institute of Health and Welfare Aust Hospital Stat 2011-12, 2013). Despite numerous available antidepressant treatments, many patients do not respond to conventional therapy, having what is called 'treatment resistance' (Fava Biol Psychiatry 53:649-659, 2003)...
November 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29147790/-etomidate-for-intravenous-induction-of-anaesthesia
#2
C Dumps, D Bolkenius, E Halbeck
The pharmacological and historical knowledge about the currently available intravenous induction hypnotics form the basis for the daily work of anesthetists. Side effects of using hypnotic induction agents must be anticipated and adequately treated. Decades of experience with using intravenous induction hypnotics have led to theoretical requirements for an ideal narcotic agent with a best possible side effect profile. In the absence of this optimal hypnotic induction agent, a careful selection of one or a combination of narcotic drugs is necessary to meet the needs of the respective risk constellation of the patient...
November 16, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/29138992/use-of-ketamine-in-elderly-patients-with-treatment-resistant-depression
#3
REVIEW
Carolina Medeiros da Frota Ribeiro, Patricio Riva-Posse
PURPOSE OF REVIEW: The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports...
November 15, 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29137928/camkii%C3%AE-expression-in-a-mouse-model-of-nmdar-hypofunction-schizophrenia-putative-roles-for-igf-1r-and-tlr4
#4
O M Ogundele, C C Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice...
November 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29136301/ketamine-for-the-acute-management-of-excited-delirium-and-agitation-in-the-prehospital-setting
#5
Kyle A Weant, Lauren M Linder, Clint A Ross
BACKGROUND: Traditional first-line therapy in the prehospital setting for the acutely agitated patient includes an antipsychotic in combination with a benzodiazepine. Recently, interest has grown regarding the use of ketamine in the prehospital setting as an attempt to overcome the limitations of the traditional medications and provide a more safe and effective therapy. This review provides an overview of the pharmacology of ketamine, evaluates the literature regarding ketamine use for prehospital agitation, and proposes an algorithm that may be used within the prehospital setting...
November 14, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29127600/a-review-of-current-and-emerging-approaches-to-pain-management-in-the-emergency-department
#6
REVIEW
Knox H Todd
INTRODUCTION: Pain is the most common symptom prompting an emergency department visit and emergency physicians are responsible for managing both acute pain and acute exacerbations of chronic pain resulting from a broad range of illnesses and injuries. The responsibility to treat must be balanced by the duty to limit harm resulting from analgesics. In recent years, opioid-related adverse effects, including overdose and deaths, have increased dramatically in the USA. In response to the US opioid crisis, emergency physicians have broadened their analgesic armamentarium to include a variety of non-opioid approaches...
December 2017: Pain and Therapy
https://www.readbyqxmd.com/read/29123660/does-perioperative-ketamine-have-a-role-in-the-prevention-of-chronic-postsurgical-pain-the-rocket-trial
#7
Stephan A Schug, Philip Peyton
Identifying operations and individuals with an increased risk of chronic postsurgical pain (CPSP) has led to significant interest in interventions with the potential to achieve primary prevention of this condition. Pharmacological prevention remains controversial with a Cochrane review identifying perioperative ketamine administration as the only intervention with possible benefit although, with only small, heterogeneous studies, the authors called for a large randomised controlled trial (RCT) to confirm the validity of this result...
November 2017: British Journal of Pain
https://www.readbyqxmd.com/read/29100819/behavioural-and-computational-methods-reveal-differential-effects-for-how-delayed-and-rapid-onset-antidepressants-effect-decision-making-in-rats
#8
Claire A Hales, Conor J Houghton, Emma S J Robinson
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients would be reflected in affective biases and decision making behaviour in rodents. The diffusion model was also used to investigate the underlying decision making processes...
October 31, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29100524/effect-of-ketamine-combined-with-magnesium-sulfate-in-neuropathic-pain-patients-ketapain-study-protocol-for-a-randomized-controlled-trial
#9
Noémie Delage, Véronique Morel, Pascale Picard, Fabienne Marcaillou, Bruno Pereira, Gisèle Pickering
BACKGROUND: Neuropathic pain is difficult to treat, and the efficacy of recommended drugs remains limited. N-methyl-D-aspartate receptors are implicated, and antagonists are a pharmacological option. Ketamine is widely used in French pain clinics, but without consensus or recommendations. Furthermore, the association of ketamine with magnesium has been poorly studied. The aim of the present study is to evaluate the benefit of ketamine with or without magnesium in refractory neuropathic pain...
November 3, 2017: Trials
https://www.readbyqxmd.com/read/29099938/nyx-2925-is-a-novel-nmda-receptor-specific-spirocyclic-%C3%AE-lactam-that-modulates-synaptic-plasticity-processes-associated-with-learning-and-memory
#10
M Amin Khan, David R Houck, Amanda L Gross, Xiao-Lei Zhang, Cassia Cearley, Torsten M Madsen, Roger A Kroes, Patric K Stanton, Jeffrey Burgdorf, Joseph R Moskal
Background: N-methyl-D-aspartate receptors (NMDAR) are one member of a family of ionotropic glutamate receptors that play a pivotal role in synaptic plasticity processes associated with learning and have become attractive therapeutic targets for diseases such as depression, anxiety, schizophrenia, and neuropathic pain. NYX-2925 ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide) is one member of a spiro--lactam-based chemical platform that mimics some of the dipyrrolidine structural features of rapastinel (formerly GLYX-13: threonine-proline-proline-threonine) and is distinct from known NMDAR agonists or antagonists such as D-cycloserine, ketamine, MK-801, kynurenic acid or ifenprodil...
November 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29050469/in-vivo-18-f-ge-179-brain-signal-does-not-show-nmda-specific-modulation-with-drug-challenges-in-rodents-and-nonhuman-primates
#11
Matthias Schoenberger, Frederick A Schroeder, Michael S Placzek, Randall L Carter, Bruce R Rosen, Jacob M Hooker, Christin Y Sander
As one of the major excitatory ion channels in the brain, NMDA receptors have been a leading research target for neuroscientists, physicians, medicinal chemists, and pharmaceutical companies for decades. Molecular imaging of NMDA receptors by means of positron emission tomography (PET) with [(18)F]GE-179 quickly progressed to clinical PET studies, but a thorough understanding of its binding specificity has been missing and has thus limited signal interpretation. Here a preclinical study with [(18)F]GE-179 in rodents and nonhuman primates (NHPs) is presented in an attempt to characterize [(18)F]GE-179 signal specificity...
November 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29049083/ketamine-and-pharmacological-imaging-use-of-functional-magnetic-resonance-imaging-to-evaluate-mechanisms-of-action
#12
Eric A Maltbie, Gopinath S Kaundinya, Leonard L Howell
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry...
December 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29034354/prefrontal-connectivity-and-glutamate-transmission-relevance-to-depression-pathophysiology-and-ketamine-treatment
#13
Chadi G Abdallah, Christopher L Averill, Ramiro Salas, Lynnette A Averill, Philip R Baldwin, John H Krystal, Sanjay J Mathew, Daniel H Mathalon
BACKGROUND: Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression, and was associated with ketamine's mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate the glutamate neurotransmission correlates of GBCr. METHODS: In study A, we used functional magnetic resonance imaging (fMRI) to compare GBCr between 22 TRD and 29 healthy control...
October 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/29030243/the-inhibition-of-the-kynurenine-pathway-prevents-behavioral-disturbances-and-oxidative-stress-in-the-brain-of-adult-rats-subjected-to-an-animal-model-of-schizophrenia
#14
Gislaine Z Réus, Indianara R T Becker, Giselli Scaini, Fabricia Petronilho, Jean P Oses, Rima Kaddurah-Daouk, Luciane B Ceretta, Alexandra I Zugno, Felipe Dal-Pizzol, João Quevedo, Tatiana Barichello
Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes...
October 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28988615/mechanism-of-synergistic-action-on-behavior-oxidative-stress-and-inflammation-following-co-treatment-with-ketamine-and-different-antidepressant-classes
#15
Gislaine Z Réus, Beatriz I Matias, Amanda L Maciel, Helena M Abelaira, Zuleide M Ignácio, Airam B de Moura, Danyela Matos, Lucineia G Danielski, Fabricia Petronilho, André F Carvalho, João Quevedo
BACKGROUND: Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist...
May 6, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28976571/ketamine-and-norketamine-stability-in-whole-blood-at-ambient-and-4%C3%A2-c-conditions
#16
Benjamin Duy Tran, Ganesh S Moorthy, Athena F Zuppa
A study was implemented to describe the pharmacokinetics (PK) of ketamine (K) and its metabolite norketamine (NK) in critically ill adults. Conducting studies in these subjects is hindered by the immediate need to process and freeze samples obtained in a busy intensive care setting. The ability to store unprocessed samples at room temperature for an extended time period would overcome this barrier. Stability and blood to plasma partitioning of K and NK were investigated in whole blood up to 120 h at room temperature and 4 °C...
October 4, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28954811/preclinical-characterization-of-r-3-3s-4s-3-fluoro-4-4-hydroxyphenyl-piperidin-1-yl-1-4-methylbenzyl-pyrrolidin-2-one-bms-986169-a-novel-intravenous-glutamate-n-methyl-d-aspartate-2b-glun2b-receptor-negative-allosteric-modulator-with-potential-in-major-depressive
#17
Linda J Bristow, Jyoti Gulia, Michael R Weed, Bettadapura N Srikumar, Yu-Wen Li, John D Graef, Pattipati S Naidu, Charulatha Sanmathi, Jayant Aher, Tanmaya Bastia, Mahesh Paschapur, Narasimharaju Kalidindi, Kuchibholta Vijaya Kumar, Thaddeus Molski, Rick Pieschl, Alda Fernandes, Jeffrey M Brown, Digavalli V Sivarao, Kimberly Newberry, Mark Bookbinder, Joseph Polino, Deborah Keavy, Amy Newton, Eric Shields, Jean Simmermacher, James Kempson, Jianqing Li, Huiping Zhang, Arvind Mathur, Raja Reddy Kallem, Meenakshee Sinha, Manjunath Ramarao, Reeba K Vikramadithyan, Srinivasan Thangathirupathy, Jayakumar Warrier, Joanne J Bronson, Richard E Olson, John E Macor, Charlie F Albright, Dalton King, Lorin A Thompson, Lawrence R Marcin, Michael Sinz
(R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (BMS-986169), and the phosphate prodrug (BMS-986163), were identified from a drug discovery effort focused on the development of novel, intravenous, glutamate N-methyl-D-aspartate 2B receptor (GluN2B) negative allosteric modulators for treatment resistant depression (TRD). BMS-986169 showed high binding affinity for the GluN2B subunit allosteric modulatory site (Ki = 4.03-6.3 nM) and selectively inhibited GluN2B receptor function in Xenopus oocytes expressing human N-methyl-D-aspartate receptor subtypes (IC50 = 24...
September 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28937692/bdnf-at-the-synapse-why-location-matters
#18
M Song, K Martinowich, F S Lee
Neurotrophic factors, a family of secreted proteins that support the growth, survival and differentiation of neurons, have been intensively studied for decades due to the powerful and diverse effects on neuronal physiology, as well as their therapeutic potential. Such efforts have led to a detailed understanding on the molecular mechanisms of neurotrophic factor signaling. One member, brain-derived neurotrophic factor (BDNF) has drawn much attention due to its pleiotropic roles in the central nervous system and implications in various brain disorders...
October 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28926001/ketamine-differential-neurophysiological-dynamics-in-functional-networks-in-the-rat-brain
#19
A Ahnaou, H Huysmans, R Biermans, N V Manyakov, W H I M Drinkenburg
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28916283/deuterated-d6-dextromethorphan-elicits-antidepressant-like-effects-in-mice
#20
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
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