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Ketamine long-term effects

Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action...
October 18, 2016: Behavioural Pharmacology
Maria Jenelyn M Alviar, Tom Hale, Monalisa Dungca
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP. OBJECTIVES: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP...
October 14, 2016: Cochrane Database of Systematic Reviews
Ruyan Wu, Hailou Zhang, Wenda Xue, Zhilu Zou, Cai Lu, Baomei Xia, Wei Wang, Gang Chen
Postpartum depression (PPD) has adverse effects on offspring and increases their vulnerability to psychiatric disorders such as depression. Akt-mTOR signaling in the hippocampus is implicated in depression but its role in the behavioral deficits in PPD offspring remains unknown. By using a prepregnancy stress model of PPD in which Balb/c females that experience chronic stress before pregnancy show long-lasting PPD-like behaviors, we tested depression-like behaviors in PPD offspring (PPD-F1) at juvenile and adult ages as well as in the second generation (PPD-F2) produced by cross of male PPD-F1 with naïve females...
September 28, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Lianyan Huang, Scott Hayes, Guang Yang
Anesthetic agents are often administered in the neonatal period, a time of rapid brain development and synaptogenesis. Mounting evidence suggests that anesthetics can disrupt neurocognitive development, particularly in cases of multiple or prolonged anesthetic exposure. Previous studies have shown that administering multiple doses of ketamine-xylazine (KX) anesthesia to neonatal mice can induce long-term changes to synaptic plasticity in the cortex, but the effect on neurocognitive function remains unclear...
September 10, 2016: Neurotoxicology and Teratology
Zarife Nigâr Özdemir-Kumral, Dilek Özbeyli, Ahmet Faruk Özdemir, M Buğra Karaaslan, Kübra Kaytaz, Mustafa F Kara, Olgu Enis Tok, Feriha Ercan, Berrak Ç Yeğen
INTRODUCTION: Despite its adverse health consequences, tobacco smoking is associated with lower incidence of several neurodegenerative and inflammatory diseases. The present study is aimed to show the effects of nicotine, major tobacco constituent, on five organs targeted by sepsis. METHODS: Male Wistar albino rats received tap water with (5 mg/kg) or without nicotine for 14 days. Under ketamine anesthesia, sepsis (n=50) was induced by ligation and punction of the cecum, while sham group (n=8) had only laparotomy...
August 3, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Heather Kang, Pojeong Park, Zuner A Bortolotto, Simon D Brandt, Tristan Colestock, Jason Wallach, Graham L Collingridge, David Lodge
To avoid legislation based on chemical structure, research chemicals, frequently used for recreational purposes, are continually being synthesized. N-Ethyl-1,2-diphenylethanamine (ephenidine) is a diarylethylamine that has recently become popular with recreational users searching for dissociative hallucinogenic effects. In the present study, the pharmacological basis of its neural actions has been investigated, initially by assessing its profile in central nervous system receptor binding assays and subsequently in targeted electrophysiological studies...
August 9, 2016: Neuropharmacology
Lynn Uhrig, David Janssen, Stanislas Dehaene, Béchir Jarraya
Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI...
November 1, 2016: NeuroImage
Lanting Huang, Xiu-Juan Yang, Ying Huang, Eve Y Sun, Mu Sun
NMDA receptors have been widely reported to be involved in the regulation of synaptic plasticity through effects on long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD have been implicated in learning and memory processes. Besides synaptic plasticity, it is known that the phenomenon of gamma oscillations is critical in cognitive functions. Synaptic plasticity has been widely studied, however it is still not clear, to what degree synaptic plasticity regulates the oscillations of neuronal networks...
2016: PloS One
Marina Perelló, David Artés, Cristina Pascuets, Elisabeth Esteban, Ana Maria Ey
STUDY DESIGN: Randomized, double-blind, placebo-controlled study, with a six-month follow-up period. OBJECTIVES: To test the hypothesis that a 72-hour dose of subanesthetic ketamine in this surgical procedure reduces postoperative morphine use; To assess if there are fewer adverse effects, if postoperative recovery is faster, if there is less peri-incisional hyperalgesia or if there is lower incidence of persistent postsurgical pain. SUMMARY OF BACKGROUND DATA: Tissue injury and high opioid requirements following posterior spinal fusion surgery produce central sensitization, which can in turn be associated with hyperalgesia and chronic pain...
July 7, 2016: Spine
Reza Akhondzadeh, Ali Ghomeishi, Sholeh Nesioonpour, Sanaz Nourizade
BACKGROUND: The efficient and secure techniques of anesthesia and sedation have always been needed for. One of these procedures is endoscopic retrograde cholangiopancreatography (ERCP), due to its painfulness and long duration, has high sensitivity. We compare the effects of propofol-fentanyl (PF) with propofol-ketamine (PK) to sedate patients undergoing ERCP. METHODS: In this clinical trial, patients were divided into two groups of 49 people. A group received a pharmaceutical combination of PK, and another group received a pharmaceutical combination of PF...
April 2016: Biomedical Journal
Lianyan Huang, Joseph Cichon, Ipe Ninan, Guang Yang
Accumulating evidence has shown that repeated exposure to general anesthesia during critical stages of brain development results in long-lasting behavioral deficits later in life. To date, there has been no effective treatment to mitigate the neurotoxic effects of anesthesia on brain development. By performing calcium imaging in the mouse motor cortex, we show that ketamine anesthesia causes a marked and prolonged reduction in neuronal activity during the period of post-anesthesia recovery. Administration of the AMPAkine drug CX546 [1-(1,4-benzodioxan-6-ylcarbonyl)piperidine] to potentiate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activity during emergence from anesthesia in mice enhances neuronal activity and prevents long-term motor learning deficits induced by repeated neonatal anesthesia...
June 22, 2016: Science Translational Medicine
Sean Sassano-Higgins, Dave Baron, Grace Juarez, Neevon Esmaili, Mark Gold
Ketamine was discovered in the 1960s and released for public use in 1970. Originally developed as a safer alternative to phencyclidine, ketamine is primarily used in clinical settings for analgesia and sedation. In recent years, other uses have been developed, including pain management and treatment of asthma and depression. Clinical use of ketamine causes dissociation and emergence delirium. These effects have led to recreational abuse. Although death from direct pharmacologic effects appears rare, the disinhibition and altered sensory perceptions caused by ketamine puts users at risk of environmental harm...
August 2016: Depression and Anxiety
P Puchalski, A Zyluk
Chronic, refractory complex regional pain syndrome remains very difficult to treat. A sub-anaesthetic low-dose ketamine has shown promise in advanced CRPS. We investigated the efficacy of ketamine in anaesthetic dosage in chronic, refractory CRPS patients that had failed available standard therapies. 5 female patients, aged a mean of 34 years with long-standing, a mean of 8 years', CRPS received ketamine in anaesthetic dosage over 10 days. The patients received 1-5 ketamine courses. The effect of gradual pain reduction was observed beginning on the 4(th)-5(th) day of treatment, associated with a decrease in the intensity of the allodynia (pain at light touch)...
June 2016: Handchirurgie, Mikrochirurgie, Plastische Chirurgie
Scott J Sherman, Miguel Estevez, Ari B Magill, Torsten Falk
Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD) patients by 5 case studies and show a long-lasting therapeutic benefit to reduce l-DOPA-induced dyskinesia (LID), improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a 'chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex...
January 2016: Case Reports in Neurology
Tegegne Bogale, Epherm Engidawork, Engida Yisma
BACKGROUND: Chewing fresh leaves of the khat plant (Catha edulis forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat on health, data are sparse with regard to the consequences of long-term khat chewing in resulting schizophrenic like symptoms. METHODS: A crude extract of khat at different doses (100 mg/kg (K (khat)100), 200 mg/kg (K200) and 400 mg/kg (K400)) were administered for experimental group of mice whereas standard (ketamine (KT) 10 mg/kg- positive controls (KT10)) and vehicle (2 % v/v Tween-80 in distilled water - negative control groups (CON)) were administered for control groups of mice daily for two months to evaluate subchronic oral administration of crude khat extract to induce schizophrenic-like symptoms in mice...
2016: BMC Complementary and Alternative Medicine
Scott T Benken, Alexandra Goncharenko
This report describes a patient case utilizing a nontraditional sedative, continuous infusion ketamine, as an alternative agent for intensive care unit (ICU) sedation. A 27-year-old female presented for neurosurgical management of a coup contrecoup injury, left temporal fracture, epidural hemorrhage (EDH), and temporal contusion leading to sustained mechanical ventilation. The patient experienced profound agitation during mechanical ventilation and developed adverse effects with all traditional sedatives: benzodiazepines, dexmedetomidine, opioids, and propofol...
May 2, 2016: Journal of Pharmacy Practice
Mary T Zanda, Paola Fadda, Cristiano Chiamulera, Walter Fratta, Liana Fattore
An increasing number of novel psychoactive substances are currently available and sold as 'legal highs' or 'research chemicals' accompanied by the indication that they are 'not for human consumption'. Among those that have emerged in the last few years, methoxetamine (MXE) owes its wide popularity to its easy access on the Internet and its reputation of being a 'safe' drug. MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl D-aspartate receptor antagonist properties...
September 2016: Behavioural Pharmacology
Nagendra S Singh, Ewelina Rutkowska, Anita Plazinska, Mohammed Khadeer, Ruin Moaddel, Krzysztof Jozwiak, Michel Bernier, Irving W Wainer
D-Serine is an endogenous NMDA receptor co-agonist that activates synaptic NMDA receptors modulating neuronal networks in the cerebral cortex and plays a key role in long-term potentiation of synaptic transmission. D-serine is associated with NMDA receptor neurotoxicity and neurodegeneration and elevated D-serine concentrations have been associated with Alzheimer's and Parkinsons' diseases and amyotrophic lateral sclerosis. Previous studies have demonstrated that the ketamine metabolites (rac)-dehydronorketamine and (2S,6S)-hydroxynorketamine decrease intracellular D-serine concentrations in a concentration dependent manner in PC-12 cells...
2016: PloS One
Amelie Soumier, Rayna M Carter, Timothy J Schoenfeld, Heather A Cameron
Virtually all antidepressant agents increase the birth of granule neurons in the adult dentate gyrus in rodents, providing a key basis for the neurogenesis hypothesis of antidepressant action. The novel antidepressant ketamine, however, shows antidepressant activity in humans within hours, far too rapid for a mechanism involving neuronal birth. Ketamine could potentially act more rapidly by enhancing maturation of new neurons born weeks earlier. To test this possibility, we assessed the effects of S-ketamine (S-(+)-ketamine hydrochloride) injection on maturation, as well as birth and survival, of new dentate gyrus granule neurons in rats, using the immediate-early gene zif268, proliferating cell nuclear antigen, and BrdU, respectively...
March 2016: ENeuro
Jaclyn Schwartz, James W Murrough, Dan V Iosifescu
Approximately one-third of patients with major depressive disorder (MDD) do not respond to existing antidepressants, and those who do generally take weeks to months to achieve a significant effect. There is a clear unmet need for rapidly acting and more efficacious treatments. We will review recent developments in the study of ketamine, an old anaesthetic agent which has shown significant promise as a rapidly acting antidepressant in treatment-resistant patients with unipolar MDD, focusing on clinically important aspects such as dose, route of administration and duration of effect...
May 2016: Evidence-based Mental Health
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