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https://www.readbyqxmd.com/read/29137186/dopaminergic-dysfunction-in-mammalian-dopamine-neurons-induced-by-simazine-neurotoxicity
#1
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/29120264/treatment-options-for-chorea
#2
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/29115391/effect-on-the-dopaminergic-metabolism-induced-by-oral-exposure-to-simazine-during-the-prepubertal-period-in-rats
#3
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
https://www.readbyqxmd.com/read/29114100/successful-treatment-of-severe-tardive-dyskinesia-with-valbenazine-including-a-patient-s-perspective
#4
Richard C Josiassen, Dawn M Filmyer, Jack Gillean, Syed Sikandar Shah, Tyler E Dietterich, Rita A Shaughnessy
BACKGROUND Tardive dyskinesia (TD) is a chronic involuntary movement disorder frequently induced by dopamine receptor blockers, particularly first-generation antipsychotics. Until recently, management of TD was restricted to lowering the dose of the current medication, switching to another medication, or using off-label treatments with insufficient evidence of efficacy. Valbenazine, a vesicular monoamine transporter-2 (VMAT2) inhibitor, became the first drug to be approved by the FDA specifically for the treatment of TD...
November 8, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29080203/deutetrabenazine-a-review-in-chorea-associated-with-huntington-s-disease
#5
Young-A Heo, Lesley J Scott
Oral deutetrabenazine (Austedo™), a reversible inhibitor of vesicular monoamine transporter type 2 (VMAT2) that is structurally related to tetrabenazine is approved for the treatment of chorea symptoms associated with Huntington's disease (HD). In the pivotal 12-week phase III FIRST-HD trial (n = 90), deutetrabenazine, at doses titrated for optimal chorea control and tolerability (maintenance dosage range 12-48 mg/day), was significantly more effective for controlling chorea in HD patients than placebo...
November 2017: Drugs
https://www.readbyqxmd.com/read/29031997/a-six-year-longitudinal-pet-study-of-11-c-dtbz-binding-to-the-vmat2-in-monkey-brain
#6
Michael R Kilbourn, Robert A Koeppe
INTRODUCTION: The longitudinal reproducibility of in vivo binding potential measures for [(11)C]dihydrotetrabenazine ([(11)C]DTBZ) binding to the vesicular monoamine transporter 2 (VMAT2) site in primate brain was examined using a unique dataset of repeated control PET imaging studies. METHODS: Forty-one dynamic [(11)C]DTBZ PET studies were completed in a single rhesus monkey. Imaging equipment (microPET P4), personnel, radiotracer characteristics (injected mass amounts, molar activity) and image data analysis (BPND-Logan) were consistent throughout the entire sequence of PET studies...
September 5, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29024264/deutetrabenazine-for-tardive-dyskinesia-a-systematic-review-of-the-efficacy-and-safety-profile-for-this-newly-approved-novel-medication-what-is-the-number-needed-to-treat-number-needed-to-harm-and-likelihood-to-be-helped-or-harmed
#7
REVIEW
Leslie Citrome
OBJECTIVE: Deutetrabenazine is a deuterated formulation of tetrabenazine. The aim of this systematic review is to describe the efficacy, tolerability and safety of deutetrabenazine for the treatment of tardive dyskinesia (TD). DATA SOURCES: The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'deutetrabenazine' OR 'SD-809', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses...
October 12, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28982631/effect-of-the-5%C3%AE-reductase-enzyme-inhibitor-dutasteride-in-the-brain-of-intact-and-parkinsonian-mice
#8
Nadhir Litim, Marc Morissette, Donatella Caruso, Roberto C Melcangi, Thérèse Di Paolo
Dutasteride is a 5alpha-reductase inhibitor in clinical use to treat endocrine conditions. The present study investigated the neuroprotective mechanisms of action of dutasteride in intact and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice using a low dose of MPTP not affecting motor activity modeling early stages of Parkinson's disease (PD). We hypothesized that dutasteride neuroprotection is due to altered steroids levels. Dutasteride pre-treatment prevented loss of striatal dopamine (DA) and its metabolite DOPAC...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28965423/treatment-of-tardive-dyskinesia-with-tetrabenazine-or-valbenazine-a-systematic-review
#9
Stanley N Caroff, Saurabh Aggarwal, Charles Yonan
Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence...
October 2, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/28963508/genetic-elimination-of-dopamine-vesicular-stocks-in-the-nigrostriatal-pathway-replicates-parkinson-s-disease-motor-symptoms-without-neuronal-degeneration-in-adult-mice
#10
Elsa Isingrini, Chloé Guinaudie, Léa C Perret, Quentin Rainer, Luc Moquin, Alain Gratton, Bruno Giros
The type 2 vesicular monoamine transporter (VMAT2), by regulating the storage of monoamines transmitters into synaptic vesicles, has a protective role against their cytoplasmic toxicity. Increasing evidence suggests that impairment of VMAT2 neuroprotection contributes to the pathogenesis of Parkinson's disease (PD). Several transgenic VMAT2 mice models have been developed, however these models lack specificity regarding the monoaminergic system targeting. To circumvent this limitation, we created VMAT2-KO mice specific to the dopamine (DA) nigrostriatal pathway to analyze VMAT2's involvement in DA depletion-induced motor features associated to PD and examine the relevance of DA toxicity in the pathogenesis of neurodegeneration...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839342/efficacy-of-valbenazine-nbi-98854-in-treating-subjects-with-tardive-dyskinesia-and-schizophrenia-or-schizoaffective-disorder
#11
John M Kane, Christoph U Correll, Grace S Liang, Joshua Burke, Christopher F O'Brien
BACKGROUND: Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. METHODS: KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers)...
August 1, 2017: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/28839340/efficacy-of-valbenazine-nbi-98854-in-treating-subjects-with-tardive-dyskinesia-and-mood-disorder
#12
Christoph U Correll, Richard C Josiassen, Grace S Liang, Joshua Burke, Christopher F O'Brien
BACKGROUND: Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. METHODS: KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers)...
August 1, 2017: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/28839339/single-dose-and-repeat-once-daily-dose-safety-tolerability-and-pharmacokinetics-of-valbenazine-in-healthy-male-subjects
#13
Rosa Luo, Haig Bozigian, Roland Jimenez, Gordon Loewen, Christopher F O'Brien
Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme...
August 1, 2017: Psychopharmacology Bulletin
https://www.readbyqxmd.com/read/28830769/plasmalogen-precursor-mitigates-striatal-dopamine-loss-in-mptp-mice
#14
Edith Miville-Godbout, Mélanie Bourque, Marc Morissette, Sara Al-Sweidi, Tara Smith, Dushmanthi Jayasinghe, Shawn Ritchie, Thérèse Di Paolo
Ethanolamine plasmalogens (PlsEtn) are a class of glycerophospholipids characterized by a vinyl-ether bond at the sn-1 position that play an important role in the structure and function of membranes. Previous reports have suggested a link between reduced blood and brain PlsEtn levels and Parkinson's disease (PD). We recently reported that the DHA containing plasmalogen precursor PPI-1011 protected striatal dopamine (DA) against MPTP toxicity in mice. In this paper, we further investigate the specificity requirements of the lipid side chains by testing the oleic acid-containing plasmalogen precursor PPI-1025...
August 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28776237/differences-in-dihydrotetrabenazine-isomer-concentrations-following-administration-of-tetrabenazine-and-valbenazine
#15
Heather Skor, Evan B Smith, Gordon Loewen, Christopher F O'Brien, Dimitri E Grigoriadis, Haig Bozigian
BACKGROUND: Tetrabenazine (TBZ) activity is thought to result from four isomeric dihydrotetrabenazine (HTBZ) metabolites ([+]-α-HTBZ, [-]-α-HTBZ, [+]-β-HTBZ, [-]-β-HTBZ). Each isomer has a unique profile of vesicular monoamine transporter 2 (VMAT2) inhibition and off-target binding. Previously published data only report total isomer (α) and (β) concentrations. We developed a method to quantify the individual HTBZ isomers in samples from patients with Huntington's disease receiving TBZ...
September 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28743955/early-synaptic-dysfunction-induced-by-%C3%AE-synuclein-in-a-rat-model-of-parkinson-s-disease
#16
Jenny-Ann Phan, Kathrine Stokholm, Justyna Zareba-Paslawska, Steen Jakobsen, Kim Vang, Albert Gjedde, Anne M Landau, Marina Romero-Ramos
Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [(11)C]dihydrotetrabenazine (DTBZ)...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699794/valbenazine-for-the-treatment-of-tardive-dyskinesia
#17
Lauren C Seeberger, Robert A Hauser
Tardive dyskinesia (TD) is a hyperkinetic movement disorder that may result from treatment with antipsychotics or other dopamine receptor blocking agents. Underlying pathophysiology is incompletely understood but since the 1970s dopamine depleting agents have been used to reduce involuntary movements. The search for safe, effective treatments for TD is ongoing. Valbenazine, a novel VMAT2 inhibitor, has recently been FDA approved for treatment of TD. Areas covered: An overview of TD, unmet medical needs and current treatment guidelines are presented...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28637871/phosphorylation-at-serine-31-targets-tyrosine-hydroxylase-to-vesicles-for-transport-along-microtubules
#18
Ana Jorge-Finnigan, Rune Kleppe, Kunwar Jung-Kc, Ming Ying, Michael Marie, Ivan Rios-Mondragon, Michael F Salvatore, Jaakko Saraste, Aurora Martinez
Tyrosine hydroxylase (TH) catalyzes the conversion of l-tyrosine into l-DOPA, which is the rate-limiting step in the synthesis of catecholamines, such as dopamine, in dopaminergergic neurons. Low dopamine levels and death of the dopaminergic neurons are hallmarks of Parkinson's disease (PD), where α-synuclein is also a key player. TH is highly regulated, notably by phosphorylation of several Ser/Thr residues in the N-terminal tail. However, the functional role of TH phosphorylation at the Ser-31 site (THSer(P)-31) remains unclear...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28627368/photoactivation-of-erk-creb-vmat2-pathway-attenuates-mpp-induced-neuronal-injury-in-a-cellular-model-of-parkinson-s-disease
#19
Xiaotong Gu, Lei Liu, Qi Shen, Da Xing
The vesicular monoamine transporter 2 (VMAT2) pumps dopamine from cytoplasm into synaptic vesicles for subsequent release, and the deficits of VMAT2 has been implicated in the dopaminergic neuronal cell loss which is considered as a typical pathological feature of Parkinson's disease (PD). Low-power laser irradiation (LPLI), a potent noninvasive physiotherapy approach, is capable of penetrating into nerve tissue to exert beneficial effects such as promoting nerve regeneration and ATP production. In the present study, we demonstrated that LPLI protects against MPP(+)-induced neurotoxicity via upregulation of VMAT2 in SH-SY5Y human dopaminergic neuroblastoma cells...
June 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28623006/a-longevity-study-with-enhancer-substances-selegiline-bpap-detected-an-unknown-tumor-manifestation-suppressing-regulation-in-rat-brain
#20
J Knoll, K Baghy, S Eckhardt, P Ferdinandy, M Garami, L G Harsing, P Hauser, Z Mervai, T Pocza, Z Schaff, D Schuler, I Miklya
AIMS: First proof to show that (-)-deprenyl/selegiline (DEP), the first selective inhibitor of MAO-B, later identified as the first β-phenylethylamine (PEA)-derived synthetic catecholaminergic activity enhancer (CAE) substance and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP), the tryptamine-derived presently known most potent, selective, synthetic enhancer substance, are specific markers of unknown enhancer-sensitive brain regulations. MAIN METHODS: Longevity study disclosing the operation of tumor-manifestation-suppressing (TMS) regulation in rat brain...
August 1, 2017: Life Sciences
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