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Michael Strupp, Ludwig Kraus, Franz Schautzer, Dan Rujescu
OBJECTIVES: Since oral betahistine has a very high first-pass effect (ca. 99%), metabolized by monoamine oxidases (MAO), the benefits of a high-dosage betahistine monotherapy were compared with those of a lower dosage of betahistine in combination with the MAO-B inhibitor (MAO-B) selegiline on the frequency of acute attacks of vertigo in patients with Menière's disease (MD). METHODS: Thirteen adults aged 40-75 years (mean 58.9 years; six females) had initially been treated with a high dosage of betahistine dihydrochloride for at least 1 year...
March 12, 2018: Journal of Neurology
Hiroko Tsunekawa, Kazue Takahata, Motoki Okano, Toshiko Ishikawa, Hiroshi Satoyoshi, Tetsuya Nishimura, Naoya Hoshino, Shizuko Muraoka
3,4-Dihydroxy-L-phenylalanine (L-Dopa) remains the most effective drug for treating the motor symptoms of Parkinson's disease (PD). However, its long-term use is limited due to motor complications such as wearing-off and dyskinesia. A clinical study in PD patients with motor complications has demonstrated that selegiline, a monoamine oxidase type B inhibitor, is effective in reducing off time without worsening dyskinesia, although another study has shown worsening dyskinesia. Here, using unilateral 6-hydroxydopamine-lesioned rats showing degeneration of nigrostriatal dopaminergic neurons and L-Dopa-induced motor complications, we determined the efficacy of selegiline in controlling L-Dopa-induced motor fluctuations and exacerbated dyskinesia...
March 8, 2018: Behavioural Brain Research
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
P Xiang, J Bu, Z Qiao, X Y Zhuo, H J Wu, M Shen
OBJECTIVES: To study the content variation of selegiline and its metabolites in urine, and based on actual cases, to explore the feasibility for the identification of methamphetamine abuse and selegiline use by chiral analysis. METHODS: The urine samples were tested by chiral separation and LC-MS/MS method using CHIROBIOTIC™ V2 chiral liquid chromatography column. The chiral analysis of methamphetamine and amphetamine were performed on the urine samples from volunteers of selegiline use and drug addicts whom suspected taking selegiline...
December 2017: Fa Yi Xue za Zhi
Peter A LeWitt, Leo Verhagen Metman, Robert Rubens, Sarita Khanna, Sherron Kell, Suneel Gupta
OBJECTIVES: Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine)...
February 9, 2018: Clinical Neuropharmacology
Éva Szökő, Tamás Tábi, Peter Riederer, László Vécsei, Kálmán Magyar
The era of MAO-B inhibitors dates back more than 50 years. It began with Kálmán Magyar's outstanding discovery of the selective inhibitor, selegiline. This compound is still regarded as the gold standard of MAO-B inhibition, although newer drugs have also been introduced to the field. It was revealed early on that selective, even irreversible inhibition of MAO-B is free from the severe side effect of the non-selective MAO inhibitors, the potentiation of tyramine, resulting in the so-called 'cheese effect'...
February 7, 2018: Journal of Neural Transmission
Rui Wang, Xiaoyue Han, Jin-Mao You, Fabiao Yu, Lingxin Chen
As new biomarkers, monoamine oxidases (MAOs) play important roles in maintaining the homeostasis of biogenic amines via catalyzing the oxidation of biogenic amines to corresponding aldehydes with the generation of reactive oxygen species (ROS). MAOs have two isoforms, MAO-A and MAO-B. MAO-A is considered to be a major factor of neuropsychiatric and depressive disorders. However, MAO-B is thought to be involved in several neurodegenerative diseases. Therefore, to explore their distinct roles in different diseases, the selective detection of MAOs is essential...
February 5, 2018: Analytical Chemistry
Alireza Abdanipour, Iraj Jafari Anarkooli, Saeed Shokri, Mehrdad Ghorbanlou, Vahid Bayati, Reza Nejatbakhsh
Oxidative stress and reactive oxygen species generation have been implicated in the pathogenesis of several neurological disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In the present study, the neuroprotective effects of selegiline against hydrogen peroxide-induced oxidative stress in hippocampus-derived neural stem cells (NSCs) were evaluated. NSCs isolated from neonatal Wistar rats were pretreated with different doses of selegiline for 48 h and then exposed to 125 µM H2O2 for 30 min...
January 2018: Biomedical Reports
Chen-Xi Ye, Yared Yohannes Melcamu, Heng-Hui Li, Jiang-Tao Cheng, Tian-Tian Zhang, Yuan-Ping Ruan, Xiao Zheng, Xin Lu, Pei-Qiang Huang
Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols...
January 29, 2018: Nature Communications
Ria Fisher, Louise Lincoln, Michael J Jackson, Vincenzo Abbate, Peter Jenner, Robert Hider, Andrew Lees, Sarah Rose
Banisteriopsis caapi (B. caapi) contains harmine, harmaline, and tetrahydroharmine, has monoamine oxidase inhibitory activity, and has reported antiparkinsonian activity in humans when imbibed as a tea; however, its effects are poorly documented. For this reason, motor function was assessed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets following administration of B. caapi extract (28.4-113.6 mg/kg; po), harmine (0.1 and 0.3 mg/kg; sc), and selegiline (10 mg/kg; sc), alone or with a submaximal dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 4-7 mg/kg)...
January 24, 2018: Phytotherapy Research: PTR
Hector Contreras-Mora, Megan A Rowland, Samantha E Yohn, Merce Correa, John D Salamone
People with depression and Parkinsonism frequently show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Tasks that assess effort-related choice are being used as animal models of these motivational symptoms. The present studies characterized the ability of monoamine oxidase (MAO) inhibitors with varying selectivity profiles to reverse the low effort bias induced by the monoamine storage inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans, and because of its selective inhibition of VMAT-2, it preferentially depletes DA at low doses...
January 5, 2018: Pharmacology, Biochemistry, and Behavior
Makoto Naoi, Wakako Maruyama, Masayo Shamoto-Nagai
Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of neuronal architecture, synaptic activity, and onset of psychiatric disorders, including depression, and antisocial aggressive impulsive behaviors. MAO-B produces hydrogen peroxide and plays a vital role in neuronal loss of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. This review presents a novel role of MAO-A and B, their substrates and inhibitors, and hydrogen peroxide in brain function and neuronal survival and death...
December 26, 2017: Journal of Neural Transmission
József Attila Szász, Viorelia Constantin, Péter Alpár Fazakas, Eszter Blényesi, Levente Gábor Grieb, Antal Balla, Mónika Sárig, Kinga Szegedi, Eszter Noémi Bartha, Szabolcs Szatmári
INTRODUCTION: Selective monoamine oxidase B inhibitors have an accurate place in therapeutical strategy of Parkinsons's disease. In the early stages of the disease, especially in younger patients with milder symptoms, the introduction of levodopa substitution could be efficacious in delaying; in advanced stages they are mainly used to treat motor complications, as an adjunct to levodopa. AIM: The evaluation of therapeutical strategies used in the neurology clinics of Tirgu Mures County Emergency Clinical Hospital in order to define the role of monoamine oxidase B inhibitors...
December 2017: Orvosi Hetilap
Anna Lesniak, Mikko Aarnio, Shanti Diwakarla, Thomas Norberg, Fred Nyberg, Torsten Gordh
AIMS: d-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for d-deprenyl in synovial membrane explants from arthritic patients. MAIN METHODS: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [3 H]d-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation...
February 1, 2018: Life Sciences
Seul Ki Yeon, Ji Won Choi, Jong-Hyun Park, Ye Rim Lee, Hyeon Jeong Kim, Su Jeong Shin, Bo Ko Jang, Siwon Kim, Yong-Sun Bahn, Gyoonhee Han, Yong Sup Lee, Ae Nim Pae, Ki Duk Park
Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50 : 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor...
January 1, 2018: Bioorganic & Medicinal Chemistry
Betül Kaya Çavuşoğlu, Begüm Nurpelin Sağlık, Yusuf Özkay, Beril İnci, Zafer Asım Kaplancıklı
A new series of thirteen 2-[(4-fluorophenyl)(4-nitrobenzyl)amino]-2-oxoethyl-1-substituted-carbodithioate derivatives (4a-4m) were synthesized and tested for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory potential by an in vitro fluorometric method. Most of the compounds have found to be selective towards MAO-B than MAO-A. Compound 4j that carrying 4-nitrophenyl piperazine moiety, was detected as the most active agent amongst all compounds with the IC50 value of 0.097 ± 0.003 µM for MAO-B while that of selegiline was 0...
February 2018: Bioorganic Chemistry
Michele Pistacchi, Manuela Gioulis, Flavio Sanson, Sandro Z Marsala
BACKGROUND: 'Wearing off' refers to the phenomenology of movement disorders in Parkinson's disease (PD) that appears early and is much commoner than generally believed. It may be present in the form of either motor symptoms or non-motor symptoms. AIM: To investigate the utility of wearing-off questionnaire (WOQ-19, Italian version) in the outpatient clinical practice to assess the suitability of different combinations of treatment, in various stages of PD. METHODS: 73 consecutive patients (58% male and 42% female) suffering from PD were recruited through the Santorso Hospital and San Martino Hospital from September 2012 to March 2014...
November 2017: Neurology India
Mutsumi Iijima, Hiroshi Mitoma, Shinichiro Uchiyama, Kazuo Kitagawa
Objective: The aim of this study was to assess quantitatively the gait disorders in the daily lives of patients with Parkinson's disease (PD) using with a newly developed portable gait rhythmogram (PGR), which has a trunk-mounted acceleration sensor and automatic gait-detection algorithm. Methods: Using the PGR, we recorded the daily walking profiles of 14 PD patients before and after the addition or increase in dose of an MAO-B inhibitor (selegiline, average dose: 4...
2017: Frontiers in Neurology
Al-Shimali M Hussain, Waleed M Renno, Hanaa L Sadek, Noura M Kayali, Aseel Al-Salem, Muddanna S Rao, Khalid M Khan
Monoamine oxidase-B (MAOB), a flavin adenine dinucleotide (FAD), is an enzyme which catalyzes the oxidation of amines. MAOB is proposed to play a major role in the pathogenesis of neurodegeneration through the production of reactive oxygen species (ROS) and neurotoxins. The present study was designed to outline the effects of the MAOB inhibitor (MAOB-I) on neuroprotection of spinal neurons, regeneration of sciatic nerve fibers, and recovery of sensory-motor functions in the sciatic nerve crush injury model...
January 2018: Neuropharmacology
Hugh H Chan, Man Kit Tse, Saravana Kumar, Lang Zhuo
We previously reported that 1,3-bisbenzylimidazolium (DBZIM) bromide was neuroprotective for the dopaminergic system in Parkinson's disease (PD) models of rodent, however the underlying mechanism was unclear. We currently further confirmed that DBZIM ameliorated the Parkinsonian motor deficit and protected the nigrostriatal tract from the neurotoxicity of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3 -MPTP) in C57Bl/6 mice. The dopaminergic degeneration in the substantia nigra par compacta (SNc) and striatum was analyzed by immunohistochemistry while the monoamine oxidase B (MAO-B) inhibition effect of DBZIM was determined by enzyme kinetics...
January 5, 2018: European Journal of Pharmacology
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