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Patrick Neiens, Angela De Simone, Anna Ramershoven, Georg Höfner, Lars Allmendinger, Klaus T Wanner
MS Binding Assays represent a label free alternative to radioligand binding assays. In this study, we present an LC-ESI-MS/MS method for the quantification of (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol ((R,R)-D-84, (R,R)-1), (S,S)-reboxetine ((S,S)-2), and (S)-citalopram ((S)-3) employed as highly selective nonlabelled reporter ligands in MS Binding Assays addressing the dopamine (DAT, (R,R)-D-84), the norepinephrine (NET, (S,S)-reboxetine), and the serotonin transporter (SERT, (S)-citalopram), respectively...
March 3, 2018: Biomedical Chromatography: BMC
Andrea Cipriani, Toshi A Furukawa, Georgia Salanti, Anna Chaimani, Lauren Z Atkinson, Yusuke Ogawa, Stefan Leucht, Henricus G Ruhe, Erick H Turner, Julian P T Higgins, Matthias Egger, Nozomi Takeshima, Yu Hayasaka, Hissei Imai, Kiyomi Shinohara, Aran Tajika, John P A Ioannidis, John R Geddes
BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder...
February 20, 2018: Lancet
Sarah C O S Padilha, Suzane Virtuoso, Fernanda S Tonin, Helena H L Borba, Roberto Pontarolo
The aim of this study is to gather evidence of head-to-head double-blind randomized-controlled trials on the efficacy and safety of available treatments for attention deficit hyperactivity disorder (ADHD) in children and adolescents. A systematic review was conducted by two independent reviewers in ten electronic databases (PROSPERO register CRD42016043239). Methodological quality of included studies was evaluated according to the Jadad scale. Network meta-analyses were performed including double-blinded head-to-head trials comparing active allopathic drugs in patients (0-18 years old) diagnosed with ADHD...
February 19, 2018: European Child & Adolescent Psychiatry
Patrick Neiens, Angela De Simone, Georg Höfner, Klaus T Wanner
In this work, we present label-free, mass-spectrometry-based binding assays (MS Binding Assays), targeting the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) in simultaneous binding experiments. Using a validated LC-ESI-MS/MS method for quantification of the selective dopamine transporter inhibitor (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol ((R,R)-D-84), the selective norepinephrine transporter inhibitor (S,S)-reboxetine, and the selective serotonin reuptake inhibitor (S)-citalopram, binding affinities at the three monoamine transporters could be characterized simultaneously in a single binding experiment...
February 16, 2018: ChemMedChem
Paul R L Matthews, Jamie Horder, Michael Pearce
BACKGROUND: Schizophrenia is frequently a chronic and disabling illness with a heterogeneous range of symptoms. The positive symptoms usually respond to antipsychotics but the cognitive and negative symptoms of schizophrenia are difficult to treat with conventional antipsychotics and significantly impact on quality of life and social outcomes. Selective noradrenaline reuptake inhibitors (NRIs) increase prefrontal dopamine and noradrenaline levels without significantly affecting subcortical dopamine levels, making them an attractive candidate for treating cognitive and negative symptoms...
January 25, 2018: Cochrane Database of Systematic Reviews
Marieke De Boeck, Lisa Dubrulle, Wim Dehaen, Jan Tytgat, Eva Cuypers
This study aims to prove that ionic liquids (ILs) can be used as extraction solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the quantification of a large group of antidepressants in whole blood samples. The sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and 60µL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole blood. Subsequently, a 5-min rotary mixing step was performed followed by centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and 10µL was injected into the LC-MS/MS...
April 1, 2018: Talanta
Magdalena Jastrzębska-Więsek, Agata Siwek, Anna Partyka, Marcin Kołaczkowski, Maria Walczak, Magdalena Smolik, Gniewomir Latacz, Katarzyna Kieć-Kononowicz, Anna Wesołowska
The effect of some antidepressants co-administered with EMD386088 in the modified forced swim test in rats was investigated. Additionally, the pharmacokinetics, metabolic stability, and the effect of EMD386088 on P450 cytochromes were determined. Intraperitoneal (i.p.) coadministration of EMD386088 (2.5 mg/kg) and imipramine (15 mg/kg), reboxetine (5 mg/kg), moclobemide (10 mg/kg), or bupropion (10 mg/kg) evoked significant antidepressant-like activity, whereas no effect was observed after joint administration of EMD386088 with s-citalopram (10 mg/kg)...
October 27, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
Tomoki W Suzuki, Masaki Tanaka
We recently found that when monkeys performed an oculomotor version of the time production task, the trial-by-trial latency of self-timed saccades was negatively correlated with pupil diameter just before the delay period (Suzuki et al., 2016). Since pupil diameter has been shown to correlate with neuronal activity in the locus coeruleus, the level of noradrenaline (NA) in the brain might regulate the subjective passage of time. To examine this, we orally administered a selective noradrenaline reuptake inhibitor (reboxetine, 0...
October 9, 2017: Neuroscience
Cassiano R A F Diniz, Murilo Rodrigues, Plínio C Casarotto, Vítor S Pereira, Carlos C Crestani, Sâmia R L Joca
Depression is a common mental disorder that affects millions of individuals worldwide. Available monoaminergic antidepressants are far from ideal since they show delayed onset of action and are ineffective in approximately 40% of patients, thus indicating the need of new and more effective drugs. ATP signaling through P2 receptors seems to play an important role in neuropathological mechanisms involved in depression, since their pharmacological or genetic inactivation induce antidepressant-like effects in the forced swimming test (FST)...
December 1, 2017: Brain Research
Yefei Sun, Yifan Liang, Yang Jiao, Jueying Lin, Huiling Qu, Junjie Xu, Chuansheng Zhao
OBJECTIVE: The aim of this study is to create a rank order of the comparative efficacy and acceptability (risk of all-cause discontinuation) of antidepressant treatment in poststroke depression (PSD) by integrating direct and indirect evidence. DESIGN: Multiple-treatments meta-analysis of randomised controlled trials. PARTICIPANTS: Patients with depression following stroke. INTERVENTIONS: 10 antidepressants and placebo in the acute treatment of PSD...
August 3, 2017: BMJ Open
Heiko Graf, Maike Wiegers, Coraline Danielle Metzger, Martin Walter, Georg Grön, Birgit Abler
We recently investigated neuromodulatory effects of the noradrenergic agent reboxetine and the dopamine receptor affine amisulpride in healthy subjects on dynamic erotic stimulus processing. Whereas amisulpride left sexual functions and neural activations unimpaired, we observed detrimental activations under reboxetine within the caudate nucleus corresponding to motivational components of sexual behavior. However, broadly impaired subjective sexual functioning under reboxetine suggested effects on further neural components...
September 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Agnieszka Pałucha-Poniewiera, Karolina Podkowa, Tomasz Lenda, Andrzej Pilc
Some clinical studies indicate that scopolamine may induce a rapid antidepressant effect. Although scopolamine is a muscarinic antagonist, it seems that not only cholinergic but also glutamatergic and GABAergic systems might be involved in the mechanism of its antidepressant activity in animal models of depression. Here, we present a set of behavioral data aimed at investigating the role of monoaminergic system activity in the mechanism of the antidepressant-like action of scopolamine in an animal model based on behavioral despair, namely, the tail suspension test (TST)...
October 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Roland W Freudenmann, Ninja Freudenmann, Bartosz Zurowski, Carlos Schönfeldt-Lecuona, Ludwig Maier, Roland E Schmieder, Christian Lange-Asschenfeldt, Maximilian Gahr
Introduction Psychiatric medications are well-known triggers of clinically relevant blood pressure changes. Therefore, we aimed at creating ranking lists for their risk of causing arterial hyper- or hypotension. Methods We analyzed 784 Summaries of Product characteristics (SmPCs, available online from "Rote Liste" or "Gelbe Liste" websites) from 105 psychiatric medications registered in adult psychiatry in Germany and extracted the standardized reported risks of increasing or decreasing arterial blood pressure...
August 2017: Deutsche Medizinische Wochenschrift
Cheng Liu, Zhi-Wei Lin, Zhao-Hui Zhou, Hong-Bin Chen
Chiral amino alcohol-copper(ii) catalysts Cu-L1c and Cu-ent-L1c were utilized to promote the diastereoselective nitroaldol reactions of chiral aldehydes (S)-3 or (R)-3 with nitromethane, which respectively led to the preferential formation of certain stereoisomer for nitro diol derivatives 4. Using this catalytic protocol, all the four stereoisomers of the antidepressant reboxetine were divergently prepared. The highest overall yield of this synthetic route reached up to 30.5% from aldehyde (S)-3.
June 27, 2017: Organic & Biomolecular Chemistry
Stefania Schiavone, Paolo Tucci, Emanuela Mhillaj, Maria Bove, Luigia Trabace, Maria Grazia Morgese
Mounting evidence suggests that depression represents a risk factor and an early manifestation of Alzheimer's disease (AD). Neuropsychiatric symptoms may derive from neurobiological changes in specific brain areas and may be considered prodromal of dementia. We have previously reported the depressive-like profile in rats receiving a single intracerebroventricular injection of soluble amyloid beta protein (ßA). Here, we verified the effect of different classes of antidepressants on the ßA-induced depressive behavior and on cortical monoamine levels...
August 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Charlotte J W Connell, Benjamin Thompson, Jason Turuwhenua, Alexa Srzich, Nicholas Gant
INTRODUCTION: Fatigue-induced impairments in the control of eye movements are detectable via reduced eye movement velocity after a bout of prolonged, strenuous exercise. Slower eye movements caused by neural fatigue within the oculomotor system can be prevented by caffeine, and the upregulation of central catecholamines may be responsible for this effect. This study explored the individual contribution of dopamine and norepinephrine to fatigue-related impairments in oculomotor control...
September 2017: Medicine and Science in Sports and Exercise
Hsiao-I Kuo, Walter Paulus, Giorgi Batsikadze, Asif Jamil, Min-Fang Kuo, Michael A Nitsche
Background: Noradrenaline is a major neuromodulator in the central nervous system, and it is involved in the pathophysiology of diverse neuropsychiatric diseases. Previous transcranial magnetic stimulation studies suggested that acute application of selective noradrenaline reuptake inhibitors enhances cortical excitability in the human brain. However, other, such like clinical effects, usually require prolonged noradrenaline reuptake inhibitor treatment, which might go along with different physiological effects...
August 1, 2017: International Journal of Neuropsychopharmacology
Niels Klarskov, Dirk Cerneus, William Sawyer, Donald Newgreen, Olivier van Till, Gunnar Lose
AIMS: To evaluate the effect on urethral pressure of reference drugs known to reduce stress urinary incontinence symptoms by different effect size and mechanisms of action on urethral musculature under four test conditions in healthy female subjects using urethral pressure reflectometry. METHODS: Healthy females aged 18-55 years were recruited by advertising for this phase 1, single site, placebo-controlled, randomized, four-period, crossover study. The interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg Reboxetine, and placebo...
January 2018: Neurourology and Urodynamics
Mingzhu Lin, Haijun Li, Yan Zhao, Enbo Cai, Hongyan Zhu, Yugang Gao, Shuangli Liu, He Yang, Lianxue Zhang, Guosheng Tang, Ruiqing Wang
Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane...
March 31, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Daniela Krause, Aye-Mu Myint, Christine Schuett, Richard Musil, Sandra Dehning, Anja Cerovecki, Michael Riedel, Volker Arolt, Markus J Schwarz, Norbert Müller
BACKGROUND: Signs of an inflammatory process have been described in major depression. METHODS: In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls...
2017: Frontiers in Psychiatry
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