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John P M Finberg, Jose M Rabey
Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong antidepressant efficacy of irreversible MAO inhibitors, their clinical use has been limited by their side effect of potentiation of the cardiovascular effects of dietary amines ("cheese effect")...
2016: Frontiers in Pharmacology
J Knoll, I Miklya
AIMS: The first longevity study demonstrating that rats treated with the MAO-B inhibitory dose of (-)-deprenyl (0.25mg/kg) lived significantly longer than their saline-treated peers was published in 1988, and corroborated in many papers. The recent findings that (-)-deprenyl is primarily a PEA-derived synthetic catecholaminergic activity enhancersubstance; (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP) is a tryptamine-derived synthetic enhancer substance, initiated our first longevity study on rats with low enhancer doses of (-)-deprenyl and BPAP to test the enhancer effect's role inlife extension...
October 21, 2016: Life Sciences
Hongxiang Sun, Xiuquan He, Cejia Liu, Lingyu Li, Ruoyu Zhou, Tianyun Jin, Su Yue, Da Feng, Jie Gong, Jiawei Sun, Jianbo Ji, Lan Xiang
Oleracein E (OE), a tetrahydroisoquinoline possessing potent anti-oxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pre-treatment with OE (10 μM, 2 h) decreased LDH release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited ERK1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation...
October 12, 2016: ACS Chemical Neuroscience
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
Xavier Castells, Ruth Cunill, Clara Pérez-Mañá, Xavier Vidal, Dolors Capellà
BACKGROUND: Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES: To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy...
September 27, 2016: Cochrane Database of Systematic Reviews
Ehsan Nabovati, Hasan Vakili-Arki, Zhila Taherzadeh, Mohammad Reza Saberi, Ameen Abu-Hanna, Saeid Eslami
The objective of this study was to determine incidence rate, type, and pattern of clinically relevant potential drug-drug interactions (pDDIs) in a large outpatient population of a developing country. A retrospective, descriptive cross-sectional study was conducted on outpatients' prescriptions in Khorasan Razavi province, Iran, over 12 months. A list of 25 clinically relevant DDIs, which are likely to occur in the outpatient setting, was used as the reference. Most frequent clinically relevant pDDIs, most common drugs contributing to the pDDIs, and the pattern of pDDIs for each medical specialty were determined...
May 2016: Research in Pharmaceutical Sciences
I Miklya
Deprenyl/Selegiline (DEP), created by Joseph Knoll in the 1960s, registered in more than 60 countries to treat Parkinson's disease, Alzheimer's disease, major depressive disorder; and used as an anti-aging drug, achieved its place in research and therapy as the first selective inhibitor of B-type monoamine oxidase (MAO-B). The demonstration that the DEP analog (-)-1-phenyl-2-propylaminopentane devoid of MAO inhibitory property, enhanced like DEP the activity of the catecholaminergic brain engine revealed that this effect is unrelated to the selective inhibition of MAO-B...
August 2, 2016: Molecular Psychiatry
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
Rani Sasidharan, Sreedharannair Leelabaiamma Manju, Gülberk Uçar, Ipek Baysal, Bijo Mathew
A series of 11 indole-based chalcones (IC1-11) with various electron donating and withdrawing groups at the para position of the phenyl ring B were synthesized. All the compounds were tested for their human monoamine oxidase (hMAO)-A and hMAO-B inhibitory potencies. Most of the synthesized candidates proved to be potent and selective inhibitors of MAO-B rather than MAO-A, with a reversible and competitive mode. Among them, compound IC9 was found to be a potent inhibitor of hMAO-B with Ki  = 0.01 ± 0...
August 2016: Archiv der Pharmazie
Hongbo Zhang, Xifan Yin, Zhiyuan Ouyang, Jing Chen, Shenghua Zhou, Changguo Zhang, Xin Pan, Shiliang Wang, Junxiang Yang, Yaoyao Feng, Ping Yu, Qiangchun Zhang
This study investigated the risk factors for freezing of gait (FOG) in the early stage of Parkinson disease in China, using a sample of 248 patients who were followed for 3 years. Part III of the Unified Parkinson Disease Rating Scale and the modified Hoehn-Yahr grading scale were used to evaluate the severity of motor symptoms. Nonmotor symptoms were assessed using the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale (HAMD), and Non-Motor Symptoms Scale (NMSS). The end-point was the presence of FOG at the end of follow-up; patients with FOG were classified as freezers...
June 2016: Medicine (Baltimore)
Asako Yoritaka, Hideo Mori, Nobutaka Hattori
BACKGROUND: Camptocormia in Parkinson's disease (PD) is unresponsive to various therapies and induced difficulties in their day-to-day life. OBJECTIVE: This study, an open trial, was aimed at assessing the efficacy of selegiline in the treatment of mild camptocormia in PD patients. METHODS: Participants were administered 5 mg of selegiline for the first 8 weeks and 7.5 mg for the second 8 weeks. RESULTS: As primary endpoints, the degree of thoracolumbar anteflexion decreased from 23...
2016: European Neurology
Rodica Lighezan, Adrian Sturza, Oana M Duicu, Raluca A Ceausu, Adrian Vaduva, Marian Gaspar, Horea Feier, Monica Vaida, Viviana Ivan, Daniel Lighezan, Danina M Muntean, Cristian Mornos
Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived H2O2 contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with and without diabetes mellitus subjected to coronary artery bypass grafting. To this aim, the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments...
March 22, 2016: Canadian Journal of Physiology and Pharmacology
Dharmendra Kumar Khatri, Archana Ramesh Juvekar
BACKGROUND: Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. OBJECTIVE: This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. MATERIALS AND METHODS: The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined...
May 2016: Pharmacognosy Magazine
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
James P Kesby, Athina Markou, Svetlana Semenova
Neurotoxic viral protein TAT may contribute to deficits in dopaminergic and cognitive function in individuals infected with human immunodeficiency virus. Transgenic mice with brain-specific doxycycline-induced TAT expression (TAT+, TAT- control) show impaired cognition. However, previously reported TAT-induced deficits in reversal learning may be compromised by initial learning deficits. We investigated the effects of TAT expression on memory retention/recall and reversal learning, and neurotransmitter function...
September 15, 2016: Behavioural Brain Research
Shayan Amiri, Hossein Amini-Khoei, Ali Mohammadi-Asl, Sakineh Alijanpour, Arya Haj-Mirzaian, Maryam Rahimi-Balaei, Ali Razmi, Carl O Olson, Mojgan Rastegar, Mehdi Mehdizadeh, Mohammad-Reza Zarrindast
Mother-infant interactions are known to be associated with the psychological well-being of an individual in adulthood. It is well accepted that emotional stress in early life, such as maternal separation (MS), leads to alterations in the neurotransmission systems of various brain regions, especially the mesolimbic dopaminergic system, and subsequently can increase the risk for development of psychiatric disorders including depression in adulthood. Selegiline is an irreversible monoamine oxidase (MAO) type B inhibitor which increases striatal dopamine levels and exerts an antidepressant effect...
September 1, 2016: Physiology & Behavior
Nicoletta Desideri, Luca Proietti Monaco, Rossella Fioravanti, Mariangela Biava, Matilde Yáñez, Stefano Alcaro, Francesco Ortuso
A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino)pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 = 10...
July 19, 2016: European Journal of Medicinal Chemistry
Kate Laver, Suzanne Dyer, Craig Whitehead, Lindy Clemson, Maria Crotty
OBJECTIVE: To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL) function in people with dementia. DESIGN: Overview of systematic reviews. METHODS: A systematic search in the Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE and PsycInfo in April 2015. Systematic reviews of randomised controlled trials conducted in people with Alzheimer's disease or dementia measuring the impact on ADL function were included...
2016: BMJ Open
Jamie Kammer, Akiko S Hosler, Emily Leckman-Westin, A Gregory DiRienzo
INTRODUCTION: Studies on the relationships between antidepressant medications and A1C, a measure of glucose levels over the past three months, have resulted in mixed findings. Most available research examined subclass effects. The current study aims to measure the association between individual antidepressant medications and A1C in a large nationally-representative dataset. METHODS: The sample of this study consists of 45,786 individuals who participated in the National Health and Nutrition Examination Survey between 1999 and 2012...
October 2016: Primary Care Diabetes
Nir Giladi, Mahnaz Asgharnejad, Lars Bauer, Frank Grieger, Babak Boroojerdi
BACKGROUND: Monoamine oxidase B (MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson's disease (PD). OBJECTIVE: To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. METHODS: In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose ≤8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks...
April 2, 2016: Journal of Parkinson's Disease
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