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https://www.readbyqxmd.com/read/29721633/decreased-vmat2-in-the-pancreas-of-humans-with-type-2-diabetes-mellitus-measured-in-vivo-by-pet-imaging
#1
Gary W Cline, Mika Naganawa, Laigao Chen, Kristin Chidsey, Santos Carvajal-Gonzalez, Sylvester Pawlak, Michelle Rossulek, Yanwei Zhang, Jason Bini, Timothy J McCarthy, Richard E Carson, Roberto A Calle
AIMS/HYPOTHESIS: The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM...
May 2, 2018: Diabetologia
https://www.readbyqxmd.com/read/29680151/vmat2-inhibitors-and-the-path-to-ingrezza-valbenazine
#2
Nicole D Harriott, John P Williams, Evan B Smith, Haig P Bozigian, Dimitri E Grigoriadis
The dopaminergic system plays a key role in the central nervous system, regulating executive function, arousal, reward, and motor control. Dysregulation of this critical monoaminergic system has been associated with diseases of the central nervous system including schizophrenia, Parkinson's disease, and disorders such as attention deficit hyperactivity disorders and addiction. Drugs that modify the dopaminergic system by modulating the activity of dopamine have been successful in demonstrating clinical efficacy by providing treatments for these diseases...
2018: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/29609698/vmat2-inhibitors-new-drugs-for-the-treatment-of-tardive-dyskinesia
#3
Anne P Kim, Danial E Baker, Terri L Levien
OBJECTIVE: To provide a review of tardive dyskinesia (TD) symptoms, etiology, pathophysiology, and treatments. DATA SOURCES: PubMed, Web of Science, ClinicalTrials. gov, and Google Scholar were searched for relevant literature using a combination of the following terms: tardive dyskinesia, treatment, management, guidelines, tetrabenazine, deutetrabenazine, and valbenazine. Sources were limited to human data. STUDY SELECTION/DATA EXTRACTION: Articles were reviewed for relevance to TD therapy...
April 1, 2018: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/29557243/tardive-dyskinesia-placing-vesicular-monoamine-transporter-type-2-vmat2-inhibitors-into-clinical-perspective
#4
Leslie Citrome
Tardive dyskinesia (TD) is an iatrogenic movement disorder caused by exposure to dopamine receptor blocking agents. Two vesicular monoamine transporter type 2 (VMAT2) inhibitors for the treatment of TD were approved by the US Food and Drug Administration in 2017: valbenazine and deutetrabenazine. Areas covered: A brief review of TD and its identification, as well as a review of older treatment interventions is provided, followed by a detailed synthesis regarding the clinical utility of valbenazine and deutetrabenazine...
April 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29555339/aah2-gene-is-not-required-for-dopamine-dependent-neurochemical-and-behavioral-abnormalities-produced-by-toxoplasma-infection-in-mouse
#5
Ross McFarland, Zi Teng Wang, Yan Jouroukhin, Ye Li, Olga Mychko, Isabelle Coppens, Jianchun Xiao, Lorraine Jones-Brando, Robert H Yolken, L David Sibley, Mikhail V Pletnikov
Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), has been associated with the increased risk for several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood. The T. gondii genome contains two aromatic amino acid hydroxylase genes (AAH1 and AAH2) that encode proteins that can produce L-DOPA. One popular hypothesis posits that these encoded enzymes might influence dopamine (DA) production and hence DA synaptic transmission, leading to neurobehavioral abnormalities in the infected host...
March 16, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29520623/study-of-vesicular-monoamine-transporter-2-in-myopic-retina-using-18-f-fp-dtbz
#6
Yu Sun, Ning Zhao, Wangyuan Liu, Miao Liu, Zizhao Ju, Jun Li, Zhen Cheng, Xingdang Liu
PURPOSE: To investigate the relationship between expression level of vesicular monoamine transporter 2 (VMAT2) and myopia, as well as the feasibility of noninvasive myopia diagnosis through imaging VMAT2 in retina by using [18 F]fluoropropyl-(+)-dihydrotetrabenazine ([18 F]FP-(+)-DTBZ). PROCEDURES: The right eyes of ten guinea pigs were deprived of vision to establish form-deprived (FD) myopia and the left eyes were untreated as the self-control eyes. The location and expression level of VMAT2 in the eyes were detected by micro-positron emission tomography (PET)/X-ray computed tomography (CT) imaging through using [18 F]FP-(+)-DTBZ...
March 8, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29519687/reprint-of-clinical-management-of-tardive-dyskinesia-five-steps-to-success
#7
REVIEW
Leslie Citrome
Tardive dyskinesia (TD) has long been thought to be a generally irreversible consequence of the use of dopamine receptor blocking agents. There is now an opportunity to successfully manage this condition with agents approved by the US Food and Drug Administration. This is important because TD has not been eliminated with the use of second-generation antipsychotics, and the expansion of antipsychotics to treat conditions other than schizophrenia has resulted in millions of additional individuals at risk for developing TD...
June 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29515354/mechanisms-of-%C3%AE-synuclein-induced-synaptopathy-in-parkinson-s-disease
#8
REVIEW
Jessika C Bridi, Frank Hirth
Parkinson's disease (PD) is characterized by intracellular inclusions of aggregated and misfolded α-Synuclein (α-Syn), and the loss of dopaminergic (DA) neurons in the brain. The resulting motor abnormalities mark the progression of PD, while non-motor symptoms can already be identified during early, prodromal stages of disease. Recent studies provide evidence that during this early prodromal phase, synaptic and axonal abnormalities occur before the degenerative loss of neuronal cell bodies. These early phenotypes can be attributed to synaptic accumulation of toxic α-Syn...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29502799/genetics-of-tardive-dyskinesia-promising-leads-and-ways-forward
#9
REVIEW
Clement C Zai, Miriam S Maes, Arun K Tiwari, Gwyneth C Zai, Gary Remington, James L Kennedy
Tardive dyskinesia (TD) is a potentially irreversible and often debilitating movement disorder secondary to chronic use of dopamine receptor blocking medications. Genetic factors have been implicated in the etiology of TD. We therefore have reviewed the most promising genes associated with TD, including DRD2, DRD3, VMAT2, HSPG2, HTR2A, HTR2C, and SOD2. In addition, we present evidence supporting a role for these genes from preclinical models of TD. The current understanding of the etiogenesis of TD is discussed in the light of the recent approvals of valbenazine and deutetrabenazine, VMAT2 inhibitors, for treating TD...
June 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29497277/review-of-deutetrabenazine-a-novel-treatment-for-chorea-associated-with-huntington-s-disease
#10
REVIEW
Marissa Dean, Victor W Sung
Deutetrabenazine was recently approved for the treatment of chorea in Huntington's disease (HD) and is the first deuterated medication that has been US Food and Drug Administration (FDA)-approved for therapeutic use. In this article, we review deutetrabenazine's drug design, pharmacokinetics, drug interactions, efficacy, adverse events, comparison with tetrabenazine, dosage, and administration. Deutetrabenazine is a deuterated form of tetrabenazine and is a vesicular monoamine transporter 2 (VMAT2) inhibitor...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29484607/treatment-of-tardive-dyskinesia-a-general-overview-with-focus-on-the-vesicular-monoamine-transporter-2-inhibitors
#11
Nicki Niemann, Joseph Jankovic
Tardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief...
April 2018: Drugs
https://www.readbyqxmd.com/read/29478746/methylphenidate-alters-monoaminergic-and-metabolic-pathways-in-the-cerebellum-of-adolescent-rats
#12
Emmanuel Quansah, Victor Ruiz-Rodado, Martin Grootveld, Tyra S C Zetterström
Abnormalities in the cerebellar circuitry have been suggested to contribute to some of the symptoms associated with attention deficit hyperactivity disorder (ADHD). The psychostimulant methylphenidate (MPH) is the major drug for treating this condition. Here, the effects of acute (2.0 mg/kg and 5.0 mg/kg) and chronic (2.0 mg/kg, twice daily for 15 days) MPH treatments were investigated in adolescent (35-40 days old) rats on monoaminergic and metabolic markers in the cerebellum. Data acquired indicates that acute MPH treatment (2...
April 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29468404/evaluation-of-pancreatic-vmat2-binding-with-active-and-inactive-enantiomers-of-18-f-fp-dtbz-in-healthy-subjects-and-patients-with-type-1-diabetes
#13
Mika Naganawa, Keunpoong Lim, Nabeel B Nabulsi, Shu-Fei Lin, David Labaree, Jim Ropchan, Kevan C Herold, Yiyun Huang, Paul Harris, Masanori Ichise, Gary W Cline, Richard E Carson
PURPOSE: Previous studies demonstrated the utility of [18 F]fluoropropyl-(+)-dihydrotetrabenazine ([18 F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [18 F]FP-(+)-DTBZ with the inactive enantiomer, [18 F]FP-(-)-DTBZ...
February 21, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29455579/vmat2-inhibitors-for-tardive-dyskinesia-practice-implications
#14
Alyssa M Peckham, Jessica A Nicewonder
Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively...
January 1, 2018: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29449008/tardive-dyskinesia-out-of-the-shadows
#15
REVIEW
Robert A Hauser, Daniel Truong
The approvals of the first two medications, valbenazine and deutetrabenazine, to treat tardive dyskinesia have ushered in a new era in neuropsychiatric care. Tardive syndromes are defined as delayed onset, persistent movement disorders or sensory phenomena that occur in association with exposure to dopamine receptor blocking agents (DRBAs). Their underlying pathophysiology remains to be fully elucidated, but clinicians can conceptualize tardive syndromes as persistent dopamine supersensitivity states. Tardive syndromes can potentially cause distress, disfigurement, embarrassment, and dysfunction, and are often permanent...
June 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29433809/future-directions-in-tardive-dyskinesia-research
#16
REVIEW
Jonathan M Meyer
Tardive dyskinesia (TD) research is at a crossroads because of renewed interest in this syndrome following the successful development and regulatory approval of two novel vesicular monoamine transport 2 (VMAT2) inhibitors. Despite these clinical advances, significant lacunae exist in the knowledge base of TD pathophysiology, prognosis, and epidemiology. Moreover, conflicting definitions of TD as either a syndrome that encompasses a broad array of related phenomena or as a specific subset of tardive syndromes are an impediment to both clinical and basic science research, and to educational efforts targeting nonspecialist clinicians...
June 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29433808/vmat2-inhibitors-for-the-treatment-of-tardive-dyskinesia
#17
REVIEW
Laura M Scorr, Stewart A Factor
Tardive dyskinesia (TD) is an often disabling hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Although initially thought to most commonly occur with typical antipsychotics, the incidence is likely similar with atypical antipsychotics and antiemetics such as metoclopramide. Increased prescribing of these agents as well as low rates of remission have contributed to a rising prevalence of TD. Although this condition was described nearly 60 years ago, it is only within the past year that two novel therapeutic agents were FDA approved...
June 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29433806/non-vmat2-inhibitor-treatments-for-the-treatment-of-tardive-dyskinesia
#18
REVIEW
Chih-Chun Lin, William G Ondo
Although VMAT2-inhibitors are now established as first-line treatment for tardive dyskinesia, not all patients respond to, or tolerate them. Numerous other agents have been adopted to treat tardive dyskinesia, but with variable results and generally lower quality methodologic reports. Amantadine is the most promising but benzodiazepines, branched chain neutral amino acids, Vitamin B6, several nutraceuticals, and botulinum toxin injections might help some patients. In all cases, better placebo controlled trials are needed before definitive recommendations can be made...
June 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29427069/new-scaffold-for-lead-compounds-to-treat-methamphetamine-use-disorders
#19
Na-Ra Lee, Guangrong Zheng, Peter A Crooks, Michael T Bardo, Linda P Dwoskin
Despite increased methamphetamine use worldwide, pharmacotherapies are not available to treat methamphetamine use disorder. The vesicular monoamine transporter-2 (VMAT2) is an important pharmacological target for discovery of treatments for methamphetamine use disorder. VMAT2 inhibition by the natural product, lobeline, reduced methamphetamine-evoked dopamine release, methamphetamine-induced hyperlocomotion, and methamphetamine self-administration in rats. Compared to lobeline, lobelane exhibited improved affinity and selectivity for VMAT2 over nicotinic acetylcholine receptors...
February 9, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29407218/membrane-cholesterol-removal-and-replenishment-affect-rat-and-monkey-brain-monoamine-transporters
#20
Marc Morissette, Nicolas Morin, Claude Rouillard, Thérèse Di Paolo
The dopamine transporter (DAT) is abundantly expressed in the striatum where it removes extracellular dopamine into the cytosol of presynaptic nerve terminals. It is the target of drugs of abuse and antidepressants. There is a loss of the DAT in Parkinson's disease affecting release of levodopa implicated in levodopa-induced dyskinesias. This study investigated the effect of cholesterol on DAT, serotonin transporter (SERT) and vesicular monoamine transporter 2 (VMAT2) in monkey and rat brains in vitro. DAT protein levels measured by Western blot remained unchanged with in vitro methyl-β-cyclodextrin (MCD) incubations to remove membrane cholesterol or with incubations to increase membrane cholesterol content...
May 1, 2018: Neuropharmacology
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