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Carla Schettino, Clemente Dato, Guglielmo Capaldo, Simone Sampaolo, Giuseppe Di Iorio, Mariarosa Ab Melone
INTRODUCTION: Rasagiline is a selective, irreversible monoamine oxidase B inhibitor that ameliorates the symptoms of Parkinson's disease (PD) by inhibiting striatal dopamine metabolism. There is also evidence that monoamine oxidase B inhibitors increase melatonin levels in the pineal gland and may have a beneficial effect on sleep disorders, which are a common feature in patients with PD. METHODS: This single-center, prospective, observational, 12-week study compared the effect of combination therapy with levodopa 200-300 mg/d + rasagiline 1 mg/d (n=19) with levodopa 200-300 mg/d alone (n=19) in the treatment of sleep disorders in patients with idiopathic PD...
2016: Neuropsychiatric Disease and Treatment
Cafer Saka
Monoamine oxidase inhibitors (MAOIs) were the first type of antidepressant developed. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. They are also used in the treatment of Parkinson's disease, tuberculosis, and several other disorders. Therefore, it is very important to develop efficient analytical methods for monitoring and management. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. In this article, analyses of MAOIs in pharmaceutical formulations and biological fluids were reviewed from 2000 to the present, including all types of chromatographic, spectrophotometric, electrophoretic, and voltammetric techniques, focusing on isoniazid, tranylcypromine, moclobemide, rasagiline, and selegiline...
October 7, 2016: Critical Reviews in Analytical Chemistry
Cheng-You Zheng, Bao-Jian Guo, Wei Cai, Wei Cui, Shing-Hung Mak, Yu-Qiang Wang, Simon Ming-Yuen Lee, Yi-Fan Han, Zai-Jun Zhang
Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl)-cognitin (B3C), a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra...
August 2016: Neural Regeneration Research
Fariborz Rahimi, Angela C Roberts, Mandar Jog
OBJECTIVES: Freezing of gait (FoG) is a challenging clinical symptom in Parkinson's disease with variable improvements in FoG with rasagiline. In this prospective, uncontrolled, pre-/post- treatment pilot study, we explore the clinical variables that contribute to this variability and those that predict improvement. PATIENTS AND METHODS: Frequency and duration of FoG, along with other standardized scales, were evaluated in 18 optimally medicated PD participants with intractable FoG, prior to and after completion of a 90-day course of 1mg daily rasagiline...
November 2016: Clinical Neurology and Neurosurgery
Guili Huang, Fei Zhu, Yuhang Chen, Shiqiang Chen, Zhonghong Liu, Xin Li, Linlin Gan, Li Zhang, Yu Yu
A simple, rapid and reliable spectrophotometry was developed to determine monoamine oxidase (MAO). In this study, 2,4-dinitrophenylhydrazine (DNPH), a classic derivatizing reagent, was used to detect MAO-dependent aldehyde production; and traditional DNPH spectrophotometry was simplified. Benzylamine and serotonin oxidation were catalyzed by MAO-B and MAO-A, respectively, to aldehydes. These were derivatized with DNPH, and the corresponding quinones were further formed by adding NaOH. These DNPH derivatives with large conjugated structures were directly measured spectrophotometrically at 465 nm and 425 nm, without the need for precipitating, washing and suspending procedures...
November 1, 2016: Analytical Biochemistry
Florian Krismer, Klaus Seppi, Gregor K Wenning, Victor Abler, Spyridon Papapetropoulos, Werner Poewe
INTRODUCTION: We provide the first characterization of the minimally clinically important difference on the Unified Multiple System Atrophy Rating Scale in patients with the parkinsonian variant of early MSA. METHODS: Data from a randomized controlled trial of rasagiline were analyzed using clinical global impression as an anchor. Because too few patients improved with treatment, analyses were limited to defining scale cutoffs that discriminated between minimal worsening and no change...
October 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Dannit Licht, Rachel Cohen, Ofer Spiegelstein, Laura Rabinovich-Guilatt, Marina Zholkovsky, Adrian Gilbert, Jennifer B Dressman, Muhammad Safadi
OBJECTIVES: While bioequivalence between enteric-coated and immediate-release formulations can be achieved in terms of AUC, gastric emptying of enteric-coated dosage forms is a stochastic event, usually leading to lower Cmax values than those observed with the corresponding immediate release. This article examines challenges of developing enteric-coated dosage forms which are bioequivalent to the corresponding immediate-release formulations in terms of both AUC and Cmax using rasagiline as a model compound...
October 2016: Journal of Pharmacy and Pharmacology
Chava Peretz, Hagar Segev, Violet Rozani, Tanya Gurevich, Baruch El-Ad, Judith Tsamir, Nir Giladi
BACKGROUND: We aimed to compare indicators of Parkinson disease (PD) progression between patients first prescribed either selegiline or rasagiline as their antiparkinsonian drugs (APDs) on the basis of real-life data. METHODS: Pharmacy data on members of a large Israeli health maintenance organization, treated as patients with PD during 2001-2012 and prescribed selegiline or rasagiline as their first APD, were analyzed. The first APD was selegiline for 349 patients (2001-2006) and rasagiline for 485 patients (2007-2012)...
September 2016: Clinical Neuropharmacology
Olivier Rascol, Robert A Hauser, Fabrizio Stocchi, Cheryl J Fitzer-Attas, Yulia Sidi, Victor Abler, C Warren Olanow
BACKGROUND: The Attenuation of Disease progression with Azilect GIven Once-daily (ADAGIO) delayed-start study demonstrated a benefit of early-start treatment with rasagiline 1 mg/day versus delayed-start treatment in PD. This follow-up study aimed to assess whether these benefits persist and the clinical progression rate during long-term naturalistic treatment. METHODS: The ADAGIO Follow-Up study was initiated approximately 26 months after completion of the ADAGIO study...
July 19, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
N V Titova, E A Katunina, N N Sotnikova
The comorbidity in Parkinson's disease (PD), which is closely related to the tolerability of antiparkinsonian drugs, is-'analyzed. The authors present the results of the studies that have confirmed the greater safety of rasagiline compared to dopamine receptor agonists in elderly patients. The effects of rasagiline, including combinations of this drug with antidepressants, on-depression in PD and the low risk,of the serotonin -syndrome caused by these combinations are considered. The studies demonstrated the effect of rasagiline on fatigue and cognitive functions in PD patients are described...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Wei Liu, Ming Lang, Moussa B H Youdim, Tamar Amit, Yewei Sun, Zaijun Zhang, Yuqiang Wang, Orly Weinreb
Current novel therapeutic approach suggests that multifunctional compounds with diverse biological properties and a single bioavailability and pharmacokinetic metabolism, will produce higher significant advantages in treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Based on this rational, a new class of cholinesterase (ChE)-monoamine oxidase (MAO) inhibitors were designed and synthesized by amalgamating the propargyl moiety of the irreversible selective MAO-B inhibitor, neuroprotective/neurorestorative anti-Parkinsonian drug, rasagiline, into the "N-methyl" position of the ChE inhibitor, anti-AD drug rivastigmine...
October 2016: Neuropharmacology
Roy G Elbers, Henk W Berendse, Gert Kwakkel
CLINICAL QUESTION: Which pharmacological and nonpharmacological interventions are associated with improvement in general, physical, or mental fatigue and minimal adverse effects in patients with Parkinson disease (PD)? BOTTOM LINE: Rasagiline, modafinil, and doxepin are associated with improvement in fatigue and are not associated with increased risk of adverse effects in patients with PD. However, the quality of evidence is limited and does not provide a clear basis for treatment decisions...
June 7, 2016: JAMA: the Journal of the American Medical Association
M Julia García-Fuster, Jesús A García-Sevilla
RATIONALE: Fas-associated death domain (FADD) is an adaptor of death receptors that can also induce anti-apoptotic actions through its phosphorylated form (p-FADD). Activation of monoamine receptors, indirect targets of classic anti-depressant drugs (ADs), reduced FADD and increased p-FADD and p-FADD/FADD ratio in brain. OBJECTIVES: To ascertain whether ADs, which indirectly regulate monoamine receptors, modulate FADD protein forms to promote anti-apoptotic actions...
August 2016: Psychopharmacology
Ian Fyfe
No abstract text is available yet for this article.
July 2016: Nature Reviews. Neurology
Georg Nuebling, Mira Hensler, Sabine Paul, Andreas Zwergal, Alexander Crispin, Stefan Lorenzl
To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication...
August 2016: Journal of Neurology
David S Goldstein, Yunden Jinsmaa, Patti Sullivan, Courtney Holmes, Irwin J Kopin, Yehonatan Sharabi
The catecholaldehyde hypothesis predicts that monoamine oxidase (MAO) inhibition should slow the progression of Parkinson's disease, by decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). Inhibiting MAO, however, diverts the fate of cytoplasmic dopamine toward potentially harmful spontaneous oxidation products, indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels. 3,4-Dihydroxyphenylethanol (hydroxytyrosol) is an abundant anti-oxidant phenol in constituents of the Mediterranean diet...
September 2016: Neurochemical Research
Rebecca E Hughes, Katarina Nikolic, Rona R Ramsay
HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs...
2016: Frontiers in Neuroscience
Mario Masellis, Shannon Collinson, Natalie Freeman, Maria Tampakeras, Joseph Levy, Amir Tchelet, Eli Eyal, Elijahu Berkovich, Rom E Eliaz, Victor Abler, Iris Grossman, Cheryl Fitzer-Attas, Arun Tiwari, Michael R Hayden, James L Kennedy, Anthony E Lang, Jo Knight
The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials...
July 2016: Brain: a Journal of Neurology
Frantisek Cibulcik, Jan Benetin, Egon Kurca, Milan Grofik, Miloslav Dvorak, Denis Richter, Vladimir Donath, Jan Kothaj, Michal Minar, Peter Valkovic
AIMS: Freezing of gait is a disabling symptom in advanced Parkinson's disease. Positive effects have been suggested with MAO-B inhibitors. We report on an open label clinical study on the efficacy of rasagiline as add-on therapy on freezing of gait and quality of life in patients with Parkinson's disease. METHODS: Forty two patients with freezing of gait were treated with 1 mg rasagiline daily as an add-on therapy. Patients were assessed at baseline and after 1, 2 and 3 months of treatment...
April 21, 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
Roxana G Burciu, Edward Ofori, Priyank Shukla, Ofer Pasternak, Jae Woo Chung, Nikolaus R McFarland, Michael S Okun, David E Vaillancourt
Rasagiline is a monoamine oxidase type B inhibitor that possesses no amphetamine-like properties, and provides symptomatic relief in early and late stages of Parkinson's disease (PD). Data in animal models of PD suggest that chronic administration of rasagiline is associated with structural changes in the substantia nigra, and raise the question whether the structure and function of the basal ganglia could be different in PD patients treated chronically with rasagiline as compared with PD patients not treated with rasagiline...
August 2016: Human Brain Mapping
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