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https://www.readbyqxmd.com/read/27890676/combined-in-vitro-and-in-silico-approaches-to-the-assessment-of-stimulant-properties-of-novel-psychoactive-substances-the-case-of-the-benzofuran-5-mapb
#1
Michelle A Sahai, Colin Davidson, George Khelashvili, Vincenzo Barrese, Neelakshi Dutta, Harel Weinstein, Jolanta Opacka-Juffry
Novel psychoactive substances (NPS) are increasingly prevalent world-wide although their pharmacological characteristics are largely unknown; those with stimulant properties, due to interactions with the dopamine transporter (DAT), have addictive potential which their users may not realise. We evaluated the binding of 1-(1-benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB) to rat striatal DAT by means of quantitative autoradiography with [(125)I]RTI-121, and the effects of 5-MAPB on electrically-evoked dopamine efflux by fast-cyclic voltammetry in rat brain slices...
November 24, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27836941/target-site-investigation-for-the-plasma-prolactin-response-mechanism-based-pharmacokinetic-pharmacodynamic-analysis-of-risperidone-and-paliperidone-in-the-rat
#2
Shinji Shimizu, Sandra M den Hoedt, Victor Mangas Sanjuan, Sinziana Cristea, Jana K Geuer, Dirk-Jan van den Berg, Robin Hartman, Francisco Bellanti, Elizabeth C M de Lange
In order to understand the drivers in the biological system response to dopamine D2 receptor antagonists, a mechanistic semi-physiologically-based (PB) pharmacokinetic-pharmacodymanic (PKPD) model was developed to describe prolactin responses to risperidone (RIS) and its active metabolite paliperidone (PAL). A microdialysis study in rats was performed to obtain detailed plasma, brain extracellular fluid (brainECF), and cerebrospinal fluid (CSF) concentrations of PAL and RIS. To assess the impact of P-gp functioning on brain distribution, experiments were performed in absence or presence of the P-glycoprotein (P-gp) inhibitor tariquidar (TQD)...
November 11, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27801563/functional-characterization-of-a-novel-series-of-biased-signaling-dopamine-d3-receptor-agonists
#3
Wei Xu, Xiaozhao Wang, Aaron M Tocker, Peng Huang, Maarten E A Reith, Lee-Yuan Liu-Chen, Amos B Smith Iii, Sandhya Kortagere
Dopamine receptors play an integral role in controlling brain physiology. Importantly sub-type selective agonists and antagonists of dopamine receptors with biased signaling properties have been successful in treating psychiatric disorders with a low incidence of side effects. To this end, we recently designed and developed SK609, a dopamine D3 receptor (D3R) selective agonist that has atypical signaling properties. SK609 has shown efficacy in reversing akinesia and reducing L-dopa-induced dyskinesia in a hemiparkinsonian rats...
November 1, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27766352/dopamine-d2-like-receptors-modulate-freezing-response-but-not-the-activation-of-hpa-axis-during-the-expression-of-conditioned-fear
#4
Amanda R de Oliveira, Adriano E Reimer, Fernando M C V Reis, Marcus L Brandão
Considering the complexity of aversive information processing and defensive response expression, a combined action of stress modulators may be required for an optimal performance during threatening situations. Dopamine is now recognized as one of the most active modulators underlying states of fear and anxiety. On the other hand, activation of hypothalamic-pituitary-adrenocortical (HPA) axis, which leads to the release of corticosterone in rodents, has been considered a key part of the stress response. The current study is an extension of prior work investigating modulatory effects of dopamine and corticosterone on conditioned fear expression...
October 20, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/27489216/ammonia-excretion-in-mytilid-mussels-is-facilitated-by-ciliary-beating
#5
J Thomsen, N Himmerkus, N Holland, F J Sartoris, M Bleich, M Tresguerres
The excretion of nitrogenous waste products in the form of ammonia (NH3) and ammonium (NH4 (+)) is a fundamental process in aquatic organisms. For mytilid bivalves, little is known about the mechanisms and sites of excretion. This study investigated the localization and the mechanisms of ammonia excretion in mytilid mussels. An Rh protein was found to be abundantly expressed in the apical cell membrane of the plicate organ, which was previously described as a solely respiratory organ. The Rh protein was also expressed in the gill, although at significantly lower concentrations, but was not detectable in mussel kidney...
August 1, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27474321/electrochemical-sensor-for-dopamine-based-on-imprinted-silica-matrix-poly-aniline-boronic-acid-hybrid-as-recognition-element
#6
Jian Li, Ning Zhang, Qingqing Sun, Zhanming Bai, Jianbin Zheng
A novel imprinted silica matrix-poly(aniline boronic acid) hybrid for electrochemical detection of dopamine (DA) was developed. Boronic acid functionalized conducting polymer was electrochemically prepared on Au electrode. The number of covalent binding sites toward DA templates was controlled by potential cycles. A precursory sol solution of ammonium fluorosilicate (as cross-linking monomer) containing DA was spin-coated on the polymer modified electrode. Under NH3 atmosphere, the hydroxyl ions were generated in the solution and catalyzed the hydrolysis of fluorosilicate to form silica matrix...
October 1, 2016: Talanta
https://www.readbyqxmd.com/read/27419218/mesocortical-dopamine-phenotypes-in-mice-lacking-the-sonic-hedgehog-receptor-cdon
#7
Michael Verwey, Alanna Grant, Nicholas Meti, Lauren Adye-White, Angelica Torres-Berrío, Veronique Rioux, Martin Lévesque, Frederic Charron, Cecilia Flores
Motivated behaviors and many psychopathologies typically involve changes in dopamine release from the projections of the ventral tegmental area (VTA) and/or the substantia nigra pars compacta (SNc). The morphogen Sonic Hedgehog (Shh) specifies fates of midbrain dopamine neurons, but VTA-specific effects of Shh signaling are also being uncovered. In this study, we assessed the role of the Shh receptor Cdon in the development of VTA and SNc dopamine neurons. We find that Cdon is expressed in the proliferating progenitor zone of the embryonic ventral midbrain and that the number of proliferating cells in this region is increased in mouse Cdon(-/-) embryos...
May 2016: ENeuro
https://www.readbyqxmd.com/read/27408789/occupancy-of-pramipexole-sifrol-at-cerebral-dopamine-d2-3-receptors-in-parkinson-s-disease-patients
#8
Angela Deutschländer, Christian la Fougère, Kai Boetzel, Nathalie L Albert, Franz-Josef Gildehaus, Peter Bartenstein, Guoming Xiong, Paul Cumming
Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0...
2016: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27356022/isozyme-specific-allosteric-regulation-of-human-sulfotransferase-1a1
#9
Ting Wang, Ian Cook, Thomas S Leyh
The human cytosolic sulfotransferases (SULTs) comprise a 13-member enzyme family that regulates the activities of hundreds, perhaps thousands, of signaling small molecules via regiospecific transfer of the sulfuryl moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and amines of acceptors. Signaling molecules regulated by sulfonation include numerous steroid and thyroid hormones, epinephrine, serotonin, and dopamine. SULT1A1, a major phase II metabolism SULT isoform, is found at a high concentration in liver and has recently been show to harbor two allosteric binding sites, each of which binds a separate and complex class of compounds: the catechins (naturally occurring polyphenols) and nonsteroidal anti-inflammatory drugs...
July 26, 2016: Biochemistry
https://www.readbyqxmd.com/read/27337045/identification-of-a-3rd-na-binding-site-of-the-glycine-transporter-glyt2
#10
Nandhitha Subramanian, Amanda J Scopelitti, Jane E Carland, Renae M Ryan, Megan L O'Mara, Robert J Vandenberg
The Na+/Cl- dependent glycine transporters GlyT1 and GlyT2 regulate synaptic glycine concentrations. Glycine transport by GlyT2 is coupled to the co-transport of three Na+ ions, whereas transport by GlyT1 is coupled to the co-transport of only two Na+ ions. These differences in ion-flux coupling determine their respective concentrating capacities and have a direct bearing on their functional roles in synaptic transmission. The crystal structures of the closely related bacterial Na+-dependent leucine transporter, LeuTAa, and the Drosophila dopamine transporter, dDAT, have allowed prediction of two Na+ binding sites in GlyT2, but the physical location of the third Na+ site in GlyT2 is unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27318552/structural-modifications-of-the-serotonin-5-ht7-receptor-agonist-n-4-cyanophenylmethyl-4-2-biphenyl-1-piperazinehexanamide-lp-211-to-improve-in%C3%A2-vitro-microsomal-stability-a-case-study
#11
Enza Lacivita, Sabina Podlewska, Luisa Speranza, Mauro Niso, Grzegorz Satała, Roberto Perrone, Carla Perrone-Capano, Andrzej J Bojarski, Marcello Leopoldo
The 5-HT7 serotonin receptor is revealing a promising target for innovative therapeutic strategies of neurodevelopmental and neuropsychiatric disorders. Here, we report the synthesis of thirty long-chain arylpiperazine analogs of the selective and brain penetrant 5-HT7 receptor agonist LP-211 (1) designed to enhance stability towards microsomal oxidative metabolism. Commonly used medicinal chemistry strategies were used (i.e., reduction of overall lipophilicity, introduction of electron-withdrawing groups, blocking of potential vulnerable sites of metabolism), and in vitro microsomal stability was tested...
September 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27224246/clinical-pharmacology-and-efficacy-of-rotigotine-neupro%C3%A2-patch-in-the-treatment-of-restless-leg-syndrome
#12
Luigi Ferini-Strambi, Sara Marelli, Andrea Galbiati
INTRODUCTION: Restless legs syndrome/Willis Ekbom disease (RLS/WED) is a sensorimotor disorder characterized by unpleasant sensations in the legs accompanied by an urge to move them, that typically occurs and tend to worsen in the evening/night or during period of inactivity. Standard medications for RLS/WED are dopamine agonists and calcium channel α-2-δ ligands. The clinical spectrum of RLS/WED is very broad, ranging from individuals suffering from the disease during limited periods up to those severely affected, with daily symptoms...
August 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27212214/heme-coordinated-histidine-residues-form-non-specific-functional-ferritin-heme-peroxidase-system-possible-and-partial-mechanistic-relevance-to-oxidative-stress-mediated-pathology-in-neurodegenerative-diseases
#13
Sajjad Esmaeili, Mohammad Reza Ashrafi Kooshk, Seyyed Mohsen Asghari, Reza Khodarahmi
Ferritin is a giant protein composed of 24 subunits which is able to sequester up to 4500 atoms of iron. We proposed two kinds of heme binding sites in mammalian ferritins and provided direct evidence for peroxidase activity of heme-ferritin, since there is the possibility that "ferritin-heme" systems display unexpected catalytic behavior like heme-containing enzymes. In the current study, peroxidase activity of heme-bound ferritin was studied using TMB(1), l-DOPA, serotonin, and dopamine, in the presence of H2O2, as oxidant substrate...
October 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27155116/a-silicon-based-implantable-microelectrode-array-for-electrophysiological-and-dopamine-recording-from-cortex-to-striatum-in-the-non-human-primate-brain
#14
Song Zhang, Yilin Song, Mixia Wang, Zhiming Zhang, Xinyi Fan, Xianteng Song, Ping Zhuang, Feng Yue, Piu Chan, Xinxia Cai
Dual-mode, multielectrode recordings have become routine in rodent neuroscience research and have recently been adapted to the non-human primate. However, robust and reliable application of acute, multielectrode recording methods in monkeys especially for deep brain nucleus research remains a challenge. In this paper, We described a low cost silicon based 16-site implantable microelectrode array (MEA) chip fabricated by standard lithography technology for in vivo test. The array was 25mm long and designed to use in non-human primate models, for electrophysiological and electrochemical recording...
November 15, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27046214/an-ultrasensitive-lysozyme-chemiluminescence-biosensor-based-on-surface-molecular-imprinting-using-ionic-liquid-modified-magnetic-graphene-oxide-%C3%AE-cyclodextrin-as-supporting-material
#15
Huimin Duan, Xiaojiao Wang, Yanhui Wang, Yuanling Sun, Jianbo Li, Chuannan Luo
In this work, ionic liquid modified Fe3O4@dopamine/graphene oxide/β-cyclodextrin (ILs-Fe3O4@DA/GO/β-CD) was used as supporting material to synthesize surface molecularly imprinted polymer (SMIP) which then was introduced into chemiluminescence (CL) to achieve an ultrasensitive and selective biosensor for determination of lysozyme (Lys). ILs and β-CD was applied to provide multiple binding sites to prepare Lys SMIP and Fe3O4@DA was designed to make the product separate easily and prevent the aggregation of GO which could improve absorption capacity for its large specific surface area...
April 28, 2016: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27020540/supramolecular-micelle-based-nucleoapzymes-for-the-catalytic-oxidation-of-dopamine-to-aminochrome
#16
H Bauke Albada, Jan Willem de Vries, Qing Liu, Eyal Golub, Niels Klement, Andreas Herrmann, Itamar Willner
Lipidated DNAzymes or a lipidated Cu(II)-complex and lipidated aptamer sequences form supramolecular assemblies of micellar nucleoapzymes for the enhanced oxidation of dopamine to aminochrome. The catalytic functions of the micellar nucleoapzymes are attributed to the concentration of the substrate, using the aptamer units, in close proximity to the active sites.
April 25, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/26976325/the-adrenergic-%C3%AE-2-antagonist-atipamezole-alters-the-behavioural-effects-of-pramipexole-and-increases-pramipexole-concentration-in-blood-plasma
#17
P N McCormick, P J Fletcher, V S Wilson, G J Remington
Pramipexole is a dopaminergic agonist used in Parkinson's disease treatment. It is thought to exert its therapeutic and side effects through actions on dopamine D3 receptors. In a recent study, we found that at doses occupying D3 but not D2 receptors pramipexole reduced locomotion and operant responding for primary and conditioned reinforcement. These effects, however, were not blocked by a D3 receptor antagonist and were present in D3 knockout mice, suggesting non-D3 receptor mechanisms. Among the next highest affinity binding sites of pramipexole are adrenergic α2 receptors...
April 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/26947759/behavioral-analysis-of-dopaminergic-activation-in-zebrafish-and-rats-reveals-similar-phenotypes
#18
Fredrik Ek, Marcus Malo, Madelene Åberg Andersson, Christoffer Wedding, Joel Kronborg, Peder Svensson, Susanna Waters, Per Petersson, Roger Olsson
Zebrafish is emerging as a complement to mammals in behavioral studies; however, there is a lack of comparative studies with rodents and humans to establish the zebrafish as a predictive translational model. Here we present a detailed phenotype evaluation of zebrafish larvae, measuring 300-3000 variables and analyzing them using multivariate analysis to identify the most important ones for further evaluations. The dopamine agonist apomorphine has previously been shown to have a complex U-shaped dose-response relationship in the variable distance traveled...
May 18, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/26941841/polydopamine-based-surface-modification-of-novel-nanoparticle-aptamer-bioconjugates-for-in-vivo-breast-cancer-targeting-and-enhanced-therapeutic-effects
#19
Wei Tao, Xiaowei Zeng, Jun Wu, Xi Zhu, Xinghua Yu, Xudong Zhang, Jinxie Zhang, Gan Liu, Lin Mei
In this study, we reported a simple polydopamine (pD)-based surface modification method to prepare novel nanoparticle-aptamer bioconjugates (Apt-pD-DTX/NPs) for in vivo tumor targeting and enhanced therapeutic effects of breast cancer. With simple preparation procedures, the new functionalized Apt-pD-DTX/NPs could maximumly increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. The dopamine polymerization and aptamer conjugation barely changed the characters of NPs...
2016: Theranostics
https://www.readbyqxmd.com/read/26926593/dopaminergic-receptor-ligand-binding-assays-based-on-molecularly-imprinted-polymers-on-quartz-crystal-microbalance-sensors
#20
Wanpen Naklua, Roongnapa Suedee, Peter A Lieberzeit
Molecularly imprinted polymers (MIPs) have been successfully applied as selective materials for assessing the binding activity of agonist and antagonist of dopamine D1 receptor (D1R) by using quartz crystal microbalance (QCM). In this study, D1R derived from rat hypothalamus was used as a template and thus self-organized on stamps. Those were pressed into an oligomer film consisting of acrylic acid: N-vinylpyrrolidone: N,N'-(1,2-dihydroxyethylene) bis-acrylamide in a ratio of 2:3:12 spin coated onto a dual electrode QCM...
July 15, 2016: Biosensors & Bioelectronics
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