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https://www.readbyqxmd.com/read/28092469/investigational-drugs-in-recent-clinical-trials-for-treatment-resistant-depression
#1
Ricardo P Garay, Carlos A Zarate, Thomas Charpeaud, Leslie Citrome, Christoph U Correll, Ahcène Hameg, Pierre-Michel Llorca
The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and US and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week...
January 16, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28087979/rapid-antidepressant-effect-of-ketamine-correlates-with-astroglial-plasticity-in-the-hippocampus
#2
Maryam Ardalan, Ali H Rafati, Jens R Nyengaard, Gregers Wegener
BACKGROUND AND PURPOSE: Astroglia contributes to the pathophysiology of major depression and the action of antidepressant drugs through modulating synaptic plasticity; therefore, present study investigated whether fast antidepressant action of ketamine is reflected in the rapid alteration of the astrocytes morphology in a genetic animal model of depression. EXPERIMENTAL APPROACH: S-Ketamine (15 mg/kg) or saline was administered as a single injection to Flinders Line (FSL/FRL) rats...
January 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28087359/the-effect-of-nmda-r-antagonism-on-simultaneously-acquired-local-field-potentials-and-tissue-oxygen-levels-in-the-brains-of-freely-moving-rats
#3
John Kealy, Sean Commins, John P Lowry
Non-competitive NMDA receptor antagonists are known to induce psychosis-like symptoms in rodents. Administration of such compounds cause behavioural effects such as memory impairment and hyperlocomotion. Additionally, drugs such as phencyclidine (PCP), ketamine and MK-801 all cause distinctive increases in striatal local field potential (LFP) in the high frequency oscillation (HFO) band in the power spectrum (140-180 Hz). Amperometric sensors provide a means to measure tissue oxygen (tO2; a BOLD-like signal) in the brains of freely-moving rats while simultaneously acquiring LFP using the same electrode...
January 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28082019/mediatory-role-of-nmda-ampa-kainate-gabaa-and-alpha2-receptors-in-topiramate-neuroprotective-effects-against-methylphenidate-induced-neurotoxicity-in-rat
#4
Majid Motaghinejad, Manijeh Motevalian, Sulai Fatima
Prolonged abuse of methylphenidate (MPH) often causes neuronal damage. Topiramate (TPM) has neuroprotective properties, but its mechanism of action remains unclear.The current study evaluates in vivo role of various doses of TPM (10, 30, 50, 70 and 100mg/kg) and its possible mechanisms against MPH-induced hippocampal oxidative stress, inflammation and apoptosis, in absence and presence of different receptor agonists and antagonists. Domoic acid (DOM) as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as ɑ2 adrenergic receptor antagonist and haloperidole (HAL) as D2 dopamine receptor antagonist was used...
January 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/28080912/comparison-of-medetomidine-ketamine-and-butorphanol-azaperone-medetomidine-in-captive-bennett-s-wallabies-macropus-rufogriseus
#5
Megan K Watson, Mary Thurber, Sathya K Chinnadurai
The objective of this study was to compare a traditional partially reversible medetomidine-ketamine sedation with a more reversible butorphanol-azaperone-medetomidine combination in Bennett's wallabies ( Macropus rufogriseus ) maintained in a zoological collection. Fourteen animals were divided into two treatment groups. Individuals in group 1 received an intramuscular (i.m.) injection of butorphanol (0.54 ± 0.05 mg/kg), azaperone (0.22 ± 0.02 mg/kg), and medetomidine (0.16 ± 0.02 mg/kg). Individuals in group 2 received an i...
December 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
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/28070653/impact-of-acute-changes-in-perfusion-index-and-blood-pressure-on-the-accuracy-of-non-invasive-continuous-hemoglobin-concentration-measurements-during-induction-of-anesthesia
#7
Junichi Saito, Masato Kitayama, Erika Amanai, Kentaro Toyooka, Kazuyoshi Hirota
PURPOSE: Several factors affect the accuracy of non-invasive continuous hemoglobin concentration (SpHb) measurements. We had previously shown an increase in the perfusion index (PI) following induction of anesthesia which was associated with an increase in the difference between SpHb and total hemoglobin (tHb) (SpHb-tHb). We hypothesized that blunting the increase in PI by maintaining blood pressure during induction of anesthesia would improve the agreement between SpHb and tHb measurements...
January 9, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28070122/ketamine-translating-mechanistic-discoveries-into-the-next-generation-of-glutamate-modulators-for-mood-disorders
#8
C A Zarate, R Machado-Vieira
No abstract text is available yet for this article.
January 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28067704/intravenous-ketamine-infusions-for-neuropathic-pain-management-a-promising-therapy-in-need-of-optimization
#9
Dermot P Maher, Lucy Chen, Jianren Mao
Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes...
January 5, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28067693/intraoperative-ketamine-reduces-immediate-postoperative-opioid-consumption-after-spinal-fusion-surgery-in-chronic-pain-patients-with-opioid-dependency-a-randomized-blinded-trial
#10
Rikke Vibeke Nielsen, Jonna Storm Fomsgaard, Hanna Siegel, Robertas Martusevicius, Lone Nikolajsen, Jørgen Berg Dahl, Ole Mathiesen
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared to placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0-24 h postoperatively...
January 6, 2017: Pain
https://www.readbyqxmd.com/read/28065587/ffpm-a-pde4-inhibitor-reverses-learning-and-memory-deficits-in-app-ps1-transgenic-mice-via-camp-pka-creb-signaling-and-anti-inflammatory-effects
#11
Haibiao Guo, Yufang Cheng, Canmao Wang, Jingang Wu, Zhengqiang Zou, Bo Niu, Hui Yu, Haitao Wang, Jiangping Xu
Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing...
January 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28063836/inhibiting-effects-of-rhynchophylline-on-methamphetamine-dependent-zebrafish-are-related-with-the-expression-of-tyrosine-hydroxylase-th
#12
Chen Zhu, Wei Liu, Chaohua Luo, Yi Liu, Chan Li, Miao Fang, Yingbo Lin, Jinying Ou, Minting Chen, Daoqi Zhu, Ken Kin-Lam Yung, Zhixian Mo
In this study, to study the effect of rhynchophylline on TH in midbrain of methamphetamine-induced conditioned place preference (CPP) adult zebrafish, place preference adult zebrafish models were established by methamphetamine (40μg/g) and the expression of TH was observed by immunohistochemistry technique and Western blot. Ketamine (150μg/g), high dose of rhynchophylline (100μg/g) group can significantly reduce the place preference; immunohistochemistry results showed that the number of TH-positive neurons in midbrain was increased in the methamphetamine model group, whereas less TH-positive neurons were found in the ketamine group and high dosage rhynchophylline group...
January 5, 2017: Fitoterapia
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
#13
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...
January 3, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28060800/alternative-analgesics-new-drugs-for-pain-seek-to-improve-on-ketamine-s-benefits
#14
Carrie Arnold
No abstract text is available yet for this article.
January 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28059998/effect-of-subchronic-exposure-to-opioids-on-the-effective-dose-of-intravenous-and-inhalation-anaesthetics
#15
Mengchan Ou, Yu Li, Yi Kang, Xiaolin Zhao, Tao Zhu
This study aimed to investigate the effect of subchronic exposure to morphine on the 50% effective dose (EC50) (median effective concentration/EC50) values of intravenous (propofol and ketamine) and inhalation (sevoflurane) anaesthetics in mice. Eight to 12-week-old male mice were administered morphine subcutaneously for 5 days to create a subchronic morphine exposure model. Control mice were injected with saline. The EC50 for righting reflex loss and tail clip reflex of general anaesthetics on the first (D1), third (D3) and seventh days (D7), after establishing a subchronic morphine exposure model, were determined...
January 2, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28058139/the-effect-of-anakinra-on-paclitaxel-induced-peripheral-neuropathic-pain-in-rats
#16
Ufuk Kuyrukluyıldız, İlke Küpeli, Zehra Bedir, Özgür Özmen, Didem Onk, Bahadır Süleyman, Renad Mammadov, Halis Süleyman
OBJECTIVE: Paclitaxel is used in the treatment of cancer, and it may cause interleukin-1 beta (IL-1β)-related peripheral neuropathic pain. While our primary aim was to investigate the analgesic efficacy of an IL-1β antagonist, a secondary outcome was to assess whether a correlation exists between analgesic effects and antioxidant activity. METHODS: A total of 24 albino Wistar male rats were divided into the following groups: paclitaxel-control, paclitaxel+50 mg kg(-1) anakinra, paclitaxel+100 mg kg(-1) anakinra and healthy group (HG)...
December 2016: Turkish Journal of Anaesthesiology and Reanimation
https://www.readbyqxmd.com/read/28057897/review-and-update-of-the-hong-kong-epilepsy-guideline-on-status-epilepticus
#17
REVIEW
E Lw Fung, B Bh Fung
Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam...
January 6, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28057557/anesthetics-inhibit-extracellular-signal-regulated-kinase1-2-phosphorylation-via-nmda-receptor-phospholipase-c-and-protein-kinase-c-in-mouse-hippocampal-slices
#18
Gao Haiying, Han Mingjie, Zhang Lingyu, Wang Qingxiang, Wang Haisong, Zhang Bingxi
BACKGROUND: Extracellular signal-regulated kinase 1/2 (ERK1/2) has been implicated in learning and memory; however, whether intravenous anesthetics modulate ERK1/2 remains unknown. The aim of this study was to examine the effect of several intravenous anesthetics on the phosphorylation of ERK1/2 in the hippocampus of adult mice. METHODS: Western blotting was used to examine cellular levels of phosphorylated and unphosphorylated ERK1/2 in mouse hippocampus slices, which were incubated with or without anesthetics including propofol, etomidate, ketamine and midazolam, a protein kinase C (PKC) activator or inhibitor, or phospholipase C (PLC) activator or inhibitor...
January 3, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28050803/access-to-controlled-medicines-for-anesthesia-and-surgical-care-in-low-income-countries-a-narrative-review-of-international-drug-control-systems-and-policies
#19
Jason W Nickerson, Katherine Pettus, Kathleen E Wheeler, Christopher Hallam, David R Bewley-Taylor, Amir Attaran, Adrian W Gelb
PURPOSE: This article describes the functioning of the international drug control system, its integration into national legislation and policy, and the collective impact on access to medicines. SOURCE: We conducted a review of the three international drug control conventions, peer-reviewed articles, and grey literature known to the authors that describes national and international drug control systems and their impact on access to controlled medicines. This review was supplemented with literature derived from a structured search of MEDLINE(®) for articles relating to medical uses of ketamine in low- and middle-income countries conducted to strengthen an advocacy campaign...
January 3, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28048330/th-ef-207a-04-a-dynamic-contrast-enhanced-cone-beam-ct-technique-for-evaluation-of-renal-functions
#20
Z Wang, J Shi, Y Yang
PURPOSE: To develop a simple but robust method for the early detection and evaluation of renal functions using dynamic contrast enhanced cone beam CT technique. METHODS: Experiments were performed on an integrated imaging and radiation research platform developed by our lab. Animals (n=3) were anesthetized with 20uL Ketamine/Xylazine cocktail, and then received 200uL injection of iodinated contrast agent Iopamidol via tail vein. Cone beam CT was acquired following contrast injection once per minute and up to 25 minutes...
June 2016: Medical Physics
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