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https://www.readbyqxmd.com/read/28811624/pupil-size-tracks-attentional-performance-in-attention-deficit-hyperactivity-disorder
#1
G Wainstein, D Rojas-Líbano, N A Crossley, X Carrasco, F Aboitiz, T Ossandón
Attention-deficit/hyperactivity disorder (ADHD) diagnosis is based on reported symptoms, which carries the potential risk of over- or under-diagnosis. A biological marker that helps to objectively define the disorder, providing information about its pathophysiology, is needed. A promising marker of cognitive states in humans is pupil size, which reflects the activity of an 'arousal' network, related to the norepinephrine system. We monitored pupil size from ADHD and control subjects, during a visuo-spatial working memory task...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807575/triple-reuptake-inhibitors-design-synthesis-and-structure-activity-relationship-of-benzylpiperidine-tetrazoles
#2
Suresh Paudel, Xiao Min, Srijan Acharya, Daulat Bikram Khadka, Goo Yoon, Kyeong-Man Kim, Seung Hoon Cheon
Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine-tetrazoles...
July 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28797665/functionalized-polymer-monoliths-with-carbamylated-amylose-for-the-enantioselective-reversed-phase-nano-liquid-chromatographic-separation-of-a-set-of-racemic-pharmaceuticals
#3
Ali Fouad, Adel A Marzouk, Samy M Ibrahim, Sobhy M El-Adl, Ashraf Ghanem
Here we report the first encapsulation of three carbamylated amylose namely R-, S- and R/S-amylose 2,3(3,5-dimethylphenylcarbamate)-6-ethylphenylcarbamate in organic polymer monolith in situ capillary columns. The columns were investigated for the enantioselective nano-liquid chromatographic separation of a set of racemic pharmaceuticals, namely, α- and β-blockers, anti-inflammatory drugs, antifungal drugs, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, antihistaminics, anticancer drugs, and antiarrhythmic drugs...
July 23, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28774856/modafinil-improves-attentional-performance-in-healthy-non-sleep-deprived-humans-at-doses-not-inducing-hyperarousal-across-species
#4
Zackary A Cope, Arpi Minassian, Dustin Kreitner, David A MacQueen, Morgane Milienne-Petiot, Mark A Geyer, William Perry, Jared W Young
The wake-promoting drug modafinil is frequently used off-label to improve cognition in psychiatric and academic populations alike. The domain-specific attentional benefits of modafinil have yet to be quantified objectively in healthy human volunteers using tasks validated for comparison across species. Further, given that modafinil is a low-affinity inhibitor for the dopamine and norepinephrine transporters (DAT/NET respectively) it is unclear if any effects are attributable to a non-specific increase in arousal, a feature of many catecholamine reuptake inhibitors (e...
August 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28771434/cutaneous-temperature-sensitivity-alteration-in-subjects-with-chronic-stroke-sequelae-pharmacological-perspectives
#5
Artur Cesar Aquino Santos, Fábio Marcon Alfieri, Linamara Rizzo Battistella
BACKGROUND: Stroke can result in body temperature sensitivity changes. This study analyzed abnormal temperature perception of patients with stroke and the use of vasoactive drugs. METHODS: A cross-sectional retrospective study was carried out consisting of 100 patients (55.6±12.9 years old), from both genres, with either hemorrhagic or ischemic stroke, with unilateral hemiplegia or hemiparesis. Subjects had axillary temperature and different temperature sensitivities of the limbs measured using a visual analog scale (VAS)...
August 3, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28757337/differentiating-physicochemical-properties-between-ndris-and-snris-clinically-important-for-the-treatment-of-adhd
#6
Panpan Wang, Tingting Fu, Xiaoyu Zhang, Fengyuan Yang, Guoxun Zheng, Weiwei Xue, Yuzong Chen, Xiaojun Yao, Feng Zhu
BACKGROUND: Drugs available for treating attention-deficit hyperactivity disorder (ADHD) are mainly selective norepinephrine (sNRIs) and dual norepinephrine-dopamine (NDRIs) reuptake inhibitors. The major problem of sNRIs lines in their delayed onset of action and partial- or non-responses, which makes NDRIs distinguished in drug efficacy. Understanding of the differential binding modes of these 2 types of drugs to their corresponding targets can give great insights into the discovery of privileged drug-like scaffolds with improved efficacy...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734777/inhibitor-mechanisms-in-the-s1-binding-site-of-the-dopamine-transporter-defined-by-multi-site-molecular-tethering-of-photoactive-cocaine-analogs
#7
Danielle Krout, Akula Bala Pramod, Rejwi Acharya Dahal, Michael J Tomlinson, Babita Sharma, James D Foster, Mu-Fa Zou, Comfort Boatang, Amy Hauck Newman, John R Lever, Roxanne A Vaughan, L Keith Henry
Dopamine transporter (DAT) blockers like cocaine and many other abused and therapeutic drugs bind and stabilize an inactive form of the transporter inhibiting reuptake of extracellular dopamine (DA). The resulting increases in DA lead to the ability of these drugs to induce psychomotor alterations and addiction, but paradoxical findings in animal models indicate that not all DAT antagonists induce cocaine-like behavioral outcomes. How this occurs is not known, but one possibility is that uptake inhibitors may bind at multiple locations or in different poses to stabilize distinct conformational transporter states associated with differential neurochemical endpoints...
July 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28734204/molecular-dynamics-of-conformation-specific-dopamine-transporter-inhibitor-complexes
#8
Bernandie Jean, Christopher K Surratt, Jeffry D Madura
The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation...
July 11, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28731336/triple-reuptake-inhibitors-as-potential-therapeutics-for-depression-and-other-disorders-design-paradigm-and-developmental-challenges
#9
Murugaiah A M Subbaiah
Although first-line antidepressants offer therapeutic benefit, about 35% of depressed patients are not adequately treated, creating a large unmet medical need. These medicines mostly enhance the synaptic levels of serotonin and/or norepinephrine. Evidence from preclinical and clinical studies implicate dopamine hypofunction in the pathophysiology of depression. Triple reuptake inhibitors (TRIs), which elevate dopamine in addition to serotonin and norepinephrine, may demonstrate greater efficacy, with the reversal of anhedonia and improved tolerability...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28720013/the-5-ht1b-serotonin-receptor-regulates-methylphenidate-induced-gene-expression-in-the-striatum-differential-effects-on-immediate-early-genes
#10
David Alter, Joel A Beverley, Ronak Patel, Carlos A Bolaños-Guzmán, Heinz Steiner
Drug combinations that include a psychostimulant such as methylphenidate (Ritalin) and a selective serotonin reuptake inhibitor such as fluoxetine are indicated in several medical conditions. Co-exposure to these drugs also occurs with "cognitive enhancer" use by individuals treated with selective serotonin reuptake inhibitors. Methylphenidate, a dopamine reuptake inhibitor, by itself produces some addiction-related gene regulation in the striatum. We have demonstrated that co-administration of selective serotonin reuptake inhibitors potentiates these methylphenidate-induced molecular effects, thus producing a more "cocaine-like" profile...
August 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28714693/stochastic-simulation-of-dopamine-neuromodulation-for-implementation-of-fluorescent-neurochemical-probes-in-the-striatal-extracellular-space
#11
Abraham G Beyene, Ian R McFarlane, Rebecca L Pinals, Markita P Landry
Imaging the dynamic behavior of neuromodulatory neurotransmitters in the extracelluar space that arise from individual quantal release events would constitute a major advance in neurochemical imaging. Spatial and temporal resolution of these highly stochastic neuromodulatory events requires concurrent advances in the chemical development of optical nanosensors selective for neuromodulators in concert with advances in imaging methodologies to capture millisecond neurotransmitter release. Herein, we develop and implement a stochastic model to describe dopamine dynamics in the extracellular space (ECS) of the brain dorsal striatum to guide the design and implementation of fluorescent neurochemical probes that record neurotransmitter dynamics in the ECS...
August 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28707591/new-generation-non-ssri-antidepressants-therapeutic-drug-monitoring-and-pharmacological-interactions-part-1-snris-smss-saris
#12
Roberto Mandrioli, Michele Protti, Laura Mercolini
BACKGROUND: New-generation antidepressants (NGAs) are the latest additions to the clinician's arsenal in the fight against depression. After the introduction of selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups followed, identified by their main mechanisms of activity: serotonin and norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators (SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and selective serotonergic antidepressants (NaSSA); norepinephrine reuptake inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors (SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists (MaSA)...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28694090/milnacipran-affects-mouse-impulsive-aggressive-and-depressive-like-behaviors-in-a-distinct-dose-dependent-manner
#13
Iku Tsutsui-Kimura, Yu Ohmura, Takayuki Yoshida, Mitsuhiro Yoshioka
Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively...
June 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28655626/differential-effects-of-perinatal-exposure-to-antidepressants-on-learning-and-memory-acoustic-startle-anxiety-and-open-field-activity-in-sprague-dawley-rats
#14
Jenna L N Sprowles, Jillian R Hufgard, Arnold Gutierrez, Rebecca A Bailey, Sarah A Jablonski, Michael T Williams, Charles V Vorhees
Most antidepressants inhibit monoamine reuptake. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) act on the 5-HT transporter (SERT) whereas norepinephrine-dopamine reuptake inhibitors (NDRIs) act on the norepinephrine and dopamine transporters. Epidemiological reports link SSRI use during pregnancy to an increased prevalence of autism spectrum disorder (ASD). We previously showed that perinatal exposure to the SSRI citalopram (CIT) results in rodent offspring that exhibit a number of behaviors consistent with an ASD-like phenotype...
October 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28655495/tranylcypromine-in-mind-part-i-review-of-pharmacology
#15
REVIEW
Sven Ulrich, Roland Ricken, Mazda Adli
It has been over 50 years since a review has focused exclusively on the monoamine oxidase (MAO) inhibitor tranylcypromine (TCP). A new review has therefore been conducted for TCP in two parts which are written to be read preferably in close conjunction: Part I - pharmacodynamics, pharmacokinetics, drug interactions, toxicology; and Part II - clinical studies with meta-analysis of controlled studies in depression, practice of TCP treatment, place in therapy. Pharmacological data of this review part I characterize TCP as an irreversible and nonselective MAO-A/B inhibitor at low therapeutic doses of 20mg/day with supplementary norepinephrine reuptake inhibition at higher doses of 40-60mg/day...
June 24, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28644892/r-modafinil-exerts-weak-effects-on-spatial-memory-acquisition-and-dentate-gyrus-synaptic-plasticity
#16
Bharanidharan Shanmugasundaram, Yogesh D Aher, Jana Aradska, Marija Ilic, Daniel Daba Feyissa, Predrag Kalaba, Nilima Y Aher, Vladimir Dragacevic, Babak Saber Marouf, Thierry Langer, Harald H Sitte, Harald Hoeger, Gert Lubec, Volker Korz
Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28629964/a-novel-heterocyclic-compound-improves-working-memory-in-the-radial-arm-maze-and-modulates-the-dopamine-receptor-d1r-in-frontal-cortex-of-the-sprague-dawley-rat
#17
Ahmed M Hussein, Yogesh D Aher, Predrag Kalaba, Nilima Y Aher, Vladimir Dragačević, Bojana Radoman, Marija Ilić, Johann Leban, Tetyana Beryozkina, Abdel Baset M A Ahmed, Ernst Urban, Thierry Langer, Gert Lubec
A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat. CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system...
June 16, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28625719/atypical-dopamine-transporter-inhibitors-r-modafinil-and-jhw-007-differentially-affect-d2-autoreceptor-neurotransmission-and-the-firing-rate-of-midbrain-dopamine-neurons
#18
Alicia J Avelar, Jianjing Cao, Amy Hauck Newman, Michael J Beckstead
Abuse of psychostimulants like cocaine that inhibit dopamine (DA) reuptake through the dopamine transporter (DAT) represents a major public health issue, however FDA-approved pharmacotherapies have yet to be developed. Recently a class of ligands termed "atypical DAT inhibitors" has gained attention due to their range of effectiveness in increasing extracellular DA levels without demonstrating significant abuse liability. These compounds not only hold promise as therapeutic agents to treat stimulant use disorders but also as experimental tools to improve our understanding of DAT function...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28619473/cocaine-adulteration
#19
REVIEW
Oliver Kudlacek, Tina Hofmaier, Anton Luf, Felix P Mayer, Thomas Stockner, Constanze Nagy, Marion Holy, Michael Freissmuth, Rainer Schmid, Harald H Sitte
Cocaine is a naturally occurring and illicitly used psychostimulant drug, which exerts its activity at monoaminergic neurotransmitter transporters. These transporters mediate the reuptake of the monoamines dopamine, serotonin and norepinephrine and are blocked by cocaine. The increase of monoamines in the extracellular space is the phenomenon underlying the drug effects that cocaine users seek. Currently, it is one of the most important illicit drugs on the European market. However, this increase in monoamines is also the underlying cause for the development of addiction and a number of severe side effects...
June 12, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28605373/modeling-fast-scan-cyclic-voltammetry-data-from-electrically-stimulated-dopamine-neurotransmission-data-using-qnsim1-0
#20
Rashed Harun, Christine M Grassi, Miranda J Munoz, Amy K Wagner
Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution...
June 5, 2017: Journal of Visualized Experiments: JoVE
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