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https://www.readbyqxmd.com/read/29141124/the-effects-of-valbenazine-in-participants-with-tardive-dyskinesia-results-of-the-1-year-kinect-3-extension-study
#1
Stewart A Factor, Gary Remington, Cynthia L Comella, Christoph U Correll, Joshua Burke, Roland Jimenez, Grace S Liang, Christopher F O'Brien
BACKGROUND: Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia. METHODS: Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period...
November 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29140741/comparative-in-vitro-study-of-11-c-methionine-and-11-c-deuterodeprenyl-uptake-in-three-human-glioma-cell-lines
#2
Elena Vasilskis, Ingrid Kreimerman, Silvia Olivera, Eduardo Savio, Henry Engler
AIM: To compare the uptake of (11)C-deuterodeprenyl ((11)C-DED) and (11)C-methionine ((11)C-MET) in three human glioma cell lines and study the relationship with glial fibrillary acid protein (GFAP) and monoamine oxidase B (MAO B) expression. (11)C-DED is used in positron emission tomography imaging as a marker of astrocytosis in various central nervous system pathologies. It binds irreversibly to MAO B, a glial dimeric enzyme with increased activity in some neurological pathologies. MATERIALS AND METHODS: Binding and internalization studies of (11)C-MET and (11)C-DED were performed in astrocytoma grade III, glioblastoma grade IV, and radio-resistant glioblastoma grade IV cells...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29140675/identification-of-novel-allosteric-modulators-of-glutamate-transporter-eaat2
#3
Sandhya Kortagere, Ole Valente Mortensen, Jingsheng Xia, William Lester, Yuhong Fang, Yellamelli V V Srikanth, Joseph M Salvino, Andreia Cristina Karklin Fontana
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis of various neurological disorders, such as stroke, brain trauma, epilepsyand neurodegenerative diseases among others. EAAT2 is the main subtype responsible for glutamate clearance in the brain, having a key role in regulating transmission and preventing excitotoxicity. Therefore, compounds that increase the expression or activity of EAAT2 have therapeutic potential for neuroprotection. Previous studies identified molecular determinants for EAAT2 transport stimulation in a structural domain that lies at the interface of the rigid trimerization domain and the central substrate binding transport domain...
November 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29139159/syntaxin1b-contributes-to-regulation-of-the-dopaminergic-system-through-gaba-transmission-in-the-cns
#4
Tomonori Fujiwara, Takefumi Kofuji, Tatsuya Mishima, Kimio Akagawa
In neuronal plasma membrane, two syntaxin isoforms, HPC-1/syntaxin1A (STX1A) and syntaxin1B (STX1B), are predominantly expressed as soluble N-ethylmaleimide-sensitive fusion attachment protein receptors, also known as t-SNAREs. We previously reported that glutamatergic and GABAergic synaptic transmission is impaired in Stx1b null mutant (Stx1b(-/-) ) mice, but is almost normal in Stx1a null mutant (Stx1a(-/-) ) mice. These observations suggested that STX1A and STX1B have distinct functions in fast synaptic transmission in the central nervous system (CNS)...
November 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29138643/interactions-of-desmethoxyyangonin-a-secondary-metabolite-from-renealmia-alpinia-with-human-monoamine-oxidase-a-and-oxidase-b
#5
Narayan D Chaurasiya, Francisco León, Yuanqing Ding, Isabel Gómez-Betancur, Dora Benjumea, Larry A Walker, Stephen J Cutler, Babu L Tekwani
Renealmia alpinia (Zingiberaceae), a medicinal plant of tropical rainforests, is used to treat snakebites and other injuries and also as a febrifuge, analgesic, antiemetic, antiulcer, and anticonvulsant. The dichloromethane extract of R. alpinia leaves showed potent inhibition of human monoamine oxidases- (MAOs-) A and B. Phytochemical studies yielded six known compounds, including pinostrobin 1, 4'-methyl ether sakuranetin 2, sakuranetin 3, pinostrobin chalcone 4, yashabushidiol A 5, and desmethoxyyangonin 6...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29137186/dopaminergic-dysfunction-in-mammalian-dopamine-neurons-induced-by-simazine-neurotoxicity
#6
Xueting Li, Jia Yu, Jianan Li, Yanping Wu, Baixiang Li
Many studies have shown that the pollutant simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine), which has been overused, inhibits the proliferation of mammalian dopaminergic cells, and affects the developmental differentiation of mammalian dopaminergic neurons. However, few studies have shown the effects of simazine on dopaminergic metabolism in these cells. Therefore, we aim to examine the metabolic effects of simazine exposure in mouse dopaminergic progenitor neurons (MN9D) at different exposure times...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29134560/neurochemical-and-neurotoxic-effects-of-mdma-ecstasy-and-caffeine-after-chronic-combined-administration-in-mice
#7
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration...
November 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29134498/vasoplegic-shock-treated-with-methylene-blue-complicated-by-severe-serotonin-syndrome
#8
Betty S Chan, Therese Becker, Angela L Chiew, Ahmed M Abdalla, Tom A Robertson, Xin Liu, Michael S Roberts, Nicholas A Buckley
INTRODUCTION: Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. However, the patient subsequently developed severe Serotonin Syndrome (SS) as a result of an interaction between serotonergic drugs and MB. CASE REPORT: A 15-year-old male developed severe vasoplegic shock 1.5 hours after overdosing on several different medications including quetiapine slow release, quetiapine immediate release, desvenlafaxine slow release, venlafaxine, amlodipine, ramipril, fluoxetine, promethazine and lithium...
November 13, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/29133700/wearing-off-a-complex-phenomenon-often-poorly-recognized-in-parkinson-s-disease-a-study-with-the-woq-19-questionnaire
#9
Michele Pistacchi, Manuela Gioulis, Flavio Sanson, Sandro Z Marsala
BACKGROUND: 'Wearing off' refers to the phenomenology of movement disorders in Parkinson's disease (PD) that appears early and is much commoner than generally believed. It may be present in the form of either motor symptoms or non-motor symptoms. AIM: To investigate the utility of wearing-off questionnaire (WOQ-19, Italian version) in the outpatient clinical practice to assess the suitability of different combinations of treatment, in various stages of PD. METHODS: 73 consecutive patients (58% male and 42% female) suffering from PD were recruited through the Santorso Hospital and San Martino Hospital from September 2012 to March 2014...
November 2017: Neurology India
https://www.readbyqxmd.com/read/29128806/emotional-disorders-induced-by-hemopressin-and-rvd-hemopressin-%C3%AE-administration-in-rats
#10
Sheila Leone, Lucia Recinella, Annalisa Chiavaroli, Sara Martinotti, Claudio Ferrante, Adriano Mollica, Giorgia Macedonio, Azzurra Stefanucci, Szabolcs Dvorácskó, Csaba Tömböly, Luciano De Petrocellis, Michele Vacca, Luigi Brunetti, Giustino Orlando
BACKGROUND: The endocannabinoid (eCB) system plays an important role in regulating emotional disorders, and is involved, directly or indirectly, in psychiatric diseases, such as anxiety and depression. Hemopressin, a hemoglobin α chain-derived peptide, and RVD-hemopressin(α), a N-terminally extended form of hemopressin, act as antagonist/inverse agonist and negative allosteric modulator of the cannabinoid 1 (CB1) receptor, respectively. METHODS: Considering the possible involvement of these peptides on emotional behaviour, the aim of our study was to investigate the behavioural effects of a single intraperitoneal (ip) injection of hemopressin (0...
June 23, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127598/gaba-uptake-inhibition-reduces-in-vivo-extraction-fraction-in-the-ventral-tegmental-area-of-long-evans-rats-measured-by-quantitative-microdialysis-under-transient-conditions
#11
Shannon L Zandy, Rueben A Gonzales
Inhibitory signaling in the ventral tegmental area (VTA) is involved in the mechanism of action for many drugs of abuse. Although drugs of abuse have been shown to alter extracellular γ-aminobutyric acid (GABA) concentration in the VTA, knowledge on how uptake mechanisms are regulated in vivo is limited. Quantitative (no-net-flux) microdialysis is commonly used to examine the extracellular concentration and clearance of monoamine neurotransmitters, however it is unclear whether this method is sensitive to changes in clearance for amino acid neurotransmitters such as GABA...
November 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29127552/mao-b-inhibitors-do-not-block-in-vivo-flortaucipir-18-f-av-1451-binding
#12
Allan K Hansen, David J Brooks, Per Borghammer
PURPOSE: Recent evidence suggests that the tau radiotracer [(18)F]THK-5351 displays high affinity for the monoamine oxidase type B (MAO-B) enzyme. Utilizing another tau-tracer, flortaucipir ([(18)F]AV-1451), we previously reported that non-demented Parkinson's disease patients show off-target binding in subcortical structures, but no appreciable cortical uptake. However, 59 % of these patients were receiving MAO-B inhibitors at the time of their scan. Here, we retrospectively investigated if MAO-B inhibitors in clinical doses affect flortaucipir binding...
November 10, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29126847/visualization-of-painful-inflammation-in-patients-with-pain-after-traumatic-ankle-sprain-using-11-c-d-deprenyl-pet-ct
#13
Mikko Aarnio, Lieuwe Appel, Mats Fredrikson, Torsten Gordh, Olof Wolf, Jens Sörensen, Måns Thulin, Magnus Peterson, Clas Linnman
BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown...
November 7, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29126727/design-synthesis-and-biochemical-evaluation-of-novel-multi-target-inhibitors-as-potential-anti-parkinson-agents
#14
Simone Carradori, Francesco Ortuso, Anél Petzer, Donatella Bagetta, Celeste De Monte, Daniela Secci, Daniela De Vita, Paolo Guglielmi, Gokhan Zengin, Abdurrahman Aktumsek, Stefano Alcaro, Jacobus P Petzer
New 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives are proposed as dual-target-directed monoamine oxidase B (MAO-B) and acetylcholinesterase (AChE) inhibitors, as well as antioxidant agents, for the treatment of neurodegenerative disorders such as Parkinson's disease. Rational molecular design, target recognition and predicted pharmacokinetic properties have been evaluated by means of molecular modelling. Based on these properties, compounds were synthesized and evaluated in vitro as MAO-B and AChE inhibitors, and compared to the activities at their corresponding isozymes, monoamine oxidase A (MAO-A) and butyrylcholinesterase (BuChE), respectively...
October 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29126721/synthesis-monoamine-oxidase-inhibition-activity-and-molecular-docking-studies-of-novel-4-hydroxy-n-benzylidene-or-1-phenylethylidene-2-h-methyl-benzyl-1-2-benzothiazine-3-carbohydrazide-1-1-dioxides
#15
Furqan Ahmad Saddique, Sumera Zaib, Saquib Jalil, Sana Aslam, Matloob Ahmad, Sadia Sultan, Humera Naz, Mazhar Iqbal, Jamshed Iqbal
Three series of 4-hydroxy-N(')-[benzylidene/1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides (9-11)a-l were synthesized and unraveled to be highly potent dual inhibitors of monoamine oxidases (MAO-A and MAO-B). All the examined compounds demonstrated IC50 values in lower micro-molar range for both MAO-A as well as MAO-B. The most active MAO-A inhibitor was 4-hydroxy-N'-(1-phenylethylidene)-2H-benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxide (9i) with an IC50 value of 0...
October 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29126252/monoamines-in-glioblastoma-complex-biology-with-therapeutic-potential
#16
Seamus Patrick Caragher, Robert Raymond Hall, Riasat Ahsan, Atique U Ahmed
Glioblastoma (GBM) is characterized by extremely poor prognoses, despite the use of gross surgical resection, alkylating chemotherapeutic agents, and radiotherapy. Evidence increasingly highlights the role of the tumor microenvironment in enabling this aggressive phenotype. Despite this interest, the role of neurotransmitters, brain-specific messengers underlying synaptic transmission, remains murky. These signaling molecules influence a complex network of molecular pathways and cellular behaviors in many CNS-resident cells including neural stem cells and progenitor cells, neurons, and glia cells...
November 4, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29120264/treatment-options-for-chorea
#17
H Bashir, J Jankovic
Chorea is defined as jerk-like movements that move randomly from one body part to another. It is due to a variety of disorders and although current symptomatic therapy is quite effective there are few etiology- or pathogenesis-targeted therapies. The aim of this review is to summarize our own experience and published evidence in the treatment of chorea. Areas covered: After evaluating current guidelines and clinical practices for chorea of all etiologies, PubMed was searched for the most recent clinical trials and reviews using the term 'chorea' cross referenced with specific drug names...
November 9, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29116368/n-acetyl-cysteine-reverses-bio-behavioural-changes-induced-by-prenatal-inflammation-adolescent-methamphetamine-exposure-and-combined-challenges
#18
Twanette Swanepoel, Marisa Möller, Brian Herbert Harvey
RATIONALE: Schizophrenia is associated with prenatal inflammation and/or postnatal stressors such as drug abuse, resulting in immune-redox dysfunction. Antioxidants may offer therapeutic benefits. OBJECTIVES: The objective of this study is to investigate N-acetyl cysteine (NAC) as a therapeutic antioxidant to reverse schizophrenia-like bio-behavioural changes in rats exposed to maternal immune activation (MIA), adolescent methamphetamine (MA) or a combination thereof...
November 8, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29116116/urinary-sulphatoxymelatonin-as-a-biomarker-of-serotonin-status-in-biogenic-amine-deficient-patients
#19
Marta Batllori, Marta Molero-Luis, Luisa Arrabal, Javier de Las Heras, Joaquín-Alejandro Fernandez-Ramos, Luis González Gutiérrez-Solana, Salvador Ibáñez-Micó, Rosario Domingo, Jaume Campistol, Aida Ormazabal, Frederic Sedel, Thomas Opladen, Basiliki Zouvelou, Roser Pons, Angels Garcia-Cazorla, Eduardo Lopez-Laso, Rafael Artuch
Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115391/effect-on-the-dopaminergic-metabolism-induced-by-oral-exposure-to-simazine-during-the-prepubertal-period-in-rats
#20
Xueting Li, Jia Yu, Yanping Wu, Baixiang Li
The herbicide simazine is widely used in agricultural and non-agricultural fields. Studies have shown that simazine inhibits the proliferation of dopaminergic cells and affects the developmental differentiation of dopamine neurons. However, little is known about the effects of simazine on dopaminergic metabolism. Therefore, the present study examined the effects of simazine on Sprague‑Dawley (SD) rats from weaning to puberty (40 days exposure). Simazine was administered orally to SD rats at doses of 0, 12...
October 20, 2017: International Journal of Molecular Medicine
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