Read by QxMD icon Read


Anne Loesche, Jana Wiese, Sven Sommerwerk, Vivienne Simon, Wolfgang Brandt, René Csuk
Drug repurposing (=drug repositioning) is an effective way to cut costs for the development of new therapeutics and to reduce the time-to-market time-span. Following this concept a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide...
September 19, 2016: European Journal of Medicinal Chemistry
Flavio A R Barbosa, Rômulo F S Canto, Sumbal Saba, Jamal Rafique, Antonio L Braga
This paper describes the synthesis and evaluation of new dihydropyrimidinone (DHPM)-derived selenoesters as potential multi-targeted agents for the treatment of Alzheimer's disease. A series of DHPM-derived selenoesters were obtained with high structural diversity through a short and modular synthetic route. The antioxidant activity was evaluated by TBARS and iron chelation assays. These compounds were also evaluated as acetylcholinesterase inhibitors (AChEi). The compounds demonstrated good antioxidant activity, since they presented excellent lipid peroxidation inhibition and good iron chelation activity...
September 13, 2016: Bioorganic & Medicinal Chemistry
Namrata Singh, Jana Hroudová, Zdeněk Fišar
Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria...
September 23, 2016: Molecular Neurobiology
Bernadet L Klaassens, Serge A R B Rombouts, Anderson M Winkler, Helene C van Gorsel, Jeroen van der Grond, Joop M A van Gerven
Psychopharmacological research, if properly designed, may offer insight into both timing and area of effect, increasing our understanding of the brain's neurotransmitter systems. For that purpose, the acute influence of the selective serotonin reuptake inhibitor citalopram (30 mg) and the acetylcholinesterase inhibitor galantamine (8 mg) was repeatedly measured in 12 healthy young volunteers with resting state functional magnetic resonance imaging (RS-fMRI). Eighteen RS-fMRI scans were acquired per subject during this randomized, double blind, placebo-controlled, crossover study...
September 13, 2016: Human Brain Mapping
Adam Kostelnik, Alexander Cegan, Miroslav Pohanka
The use of a cell phone as a detection system is easy, simple and does not require trained personnel, which is in contrast to standard laboratory instruments. This paper deals with immobilization of acetylcholinesterase (AChE) in a gelatin matrix, and phenol red, as an indicator of AChE activity, is used in order to establish a method that is easily compatible with a camera device. AChE splits acetylcholine into choline and acetic acid, which changes the pH of a medium, resulting in a phenol red color change...
2016: Sensors
Angelo M Reggiani, Elena Simoni, Roberta Caporaso, Johann Meunier, Emeline Keller, Tangui Maurice, Anna Minarini, Michela Rosini, Andrea Cavalli
Alzheimer's disease (AD) is a chronic pathological condition that leads to neurodegeneration, loss of intellectual abilities, including cognition and memory, and ultimately to death. It is widely recognized that AD is a multifactorial disease, where different pathological cascades (mainly amyloid and tau) contribute to neural death and to the clinical outcome related to the disease. The currently available drugs for AD were developed according to the one-target, one-drug paradigm. In recent times, multi-target strategies have begun to play an increasingly central role in the discovery of more efficacious candidates for complex neurological conditions, including AD...
2016: Scientific Reports
Nurcan Karaman, Yusuf Sıcak, Tuğba Taşkın-Tok, Mehmet Öztürk, Ayşegül Karaküçük-İyidoğan, Miris Dikmen, Bedia Koçyiğit-Kaymakçıoğlu, Emine Elçin Oruç-Emre
Hydrazones and the piperidine ring containing compounds were considered as beneficial substrates in drug design. Therefore, this study was aimed at the synthesis of new benzoyl hydrazones derived from ethyl 4-oxopiperidine-1-carboxylate and 2,6-diphenylpiperidin-4-one. The synthesized compounds (1-19) were screened for their antioxidant, anticholinesterase and anticancer activities. The antioxidant capacity of the compounds was evaluated by using four complementary tests. The results showed that compound 7 and 17 have the higher lipid peroxidation inhibitory activity than the other compounds...
August 20, 2016: European Journal of Medicinal Chemistry
Dorothea Kaufmann, Anudeep Kaur Dogra, Ahmad Tahrani, Florian Herrmann, Michael Wink
Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's Disease (AD). In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM) plants were tested for their in vitro anti-acetylcholinesterase activity based on Ellman's colorimetric assay. All three extracts of Berberis bealei (formerly Mahonia bealei), Coptis chinensis and Phellodendron chinense, which contain numerous isoquinoline alkaloids, substantially inhibited AChE...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shubham Misra, Kanwaljit Chopra, Uma Nahar Saikia, Vivek Ranjan Sinha, Rakesh Sehgal, Manish Modi, Bikash Medhi
AIM: The present study investigated the efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in combination with galantamine hydrobromide-loaded solid lipid nanoparticles (GH-SLNs) in intracerebroventricular (ICV)-isoproterenol-induced rat model of Alzheimer's disease. MATERIALS & METHODS: BM-MSCs were harvested by dissecting femur and tibia of 8-10-week-old Wistar rats. 1 × 10(6) cells were administered intravenously once in ICV-isoproterenol-induced rats followed by GH-SLNs (5 mg/kg) for 3 weeks...
October 2016: Regenerative Medicine
Sulunay Parlar, Gulsah Bayraktar, Ayse Hande Tarikogullari, Vildan Alptüzün, Ercin Erciyas
A series of pyridinium salts bearing alkylphenyl groups at 1 position and hydrazone structure at 4 position of the pyridinium ring were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The cholinesterase (ChE) inhibitory activity studies were carried out by using the Ellman's colorimetric method. All compounds displayed considerable AChE and BuChE inhibitory activity and some of the compounds manifested remarkable anti-AChE activity compared to the reference compound, galantamine...
2016: Chemical & Pharmaceutical Bulletin
Nozomi Hishikawa, Yusuke Fukui, Kota Sato, Yasuyuki Ohta, Toru Yamashita, Koji Abe
AIM: The coexistence of Alzheimer's disease (AD) and cerebrovascular disease pathology increases age-dependently. We comprehensively analyzed the clinical effects of galantamine or cilostazol monotherapy to the add-on combination therapy on three major factors of dementia, such as cognitive, affective and activities of daily living functions in AD patients with asymptomatic lacunar infarction. METHODS: We divided 101 AD patients with asymptomatic lacunar infarction into two subgroups: group A (n = 61, first treated with galantamine and then cilostazol added) and group B (n = 40, first treated with cilostazol and galantamine added)...
August 31, 2016: Geriatrics & Gerontology International
Anat Fisher, Greg Carney, Ken Bassett, Neena L Chappell
BACKGROUND: In October 2007, British Columbia started to cover the cost of cholinesterase inhibitors (ChEIs)-donepezil, galantamine, and rivastigmine-for patients with mild to moderate dementia and prominent Alzheimer's disease. OBJECTIVES: To examine the impact of this policy on persistence with ChEIs. METHODS: A population-based cohort study was conducted using British Columbia administrative health data. We examined 45,537 new ChEI users aged 40 years and older between 2001 and 2012; 20,360 (45%) started the treatment after the coverage policy was launched...
July 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Georgi Stavrakov, Irena Philipova, Dimitrina Zheleva, Mariyana Atanasova, Spiro Konstantinov, Irini Doytchinova
The enzyme acetylcholinesterase is a key target in the treatment of Alzheimer's disease because of its ability to hydrolyze acetylcholine via the catalytic binding site and to accelerate the aggregation of amyloid-β peptide via the peripheral anionic site (PAS). Using docking-based predictions, in the present study we design 20 novel galantamine derivatives with alkylamide spacers of different length ending with aromatic fragments. The galantamine moiety blocks the catalytic site, while the terminal aromatic fragments bind in PAS...
July 2016: Molecular Informatics
Daniela Galimberti, Elio Scarpini
INTRODUCTION: To date, pharmacological treatment of Alzheimer's disease (AD) includes Acetylcholinesterase Inhibitors (AChEIs) for mild-to-moderate AD, and memantine for moderate-to-severe AD. AChEIs reversibly inhibit acetylcholinesterase (AChE), thus increasing the availability of acetylcholine in cholinergic synapses, enhancing cholinergic transmission. These drugs provide symptomatic short-term benefits, without clearly counteracting the progression of the disease. AREAS COVERED: On the wake of successful clinical trials which lead to the marketing of AChEIs donepezil, rivastigmine and galantamine, many compounds with AChEI properties have been developed and tested mainly in Phase I-II clinical trials in the last twenty years...
October 2016: Expert Opinion on Investigational Drugs
Agnieszka Nikiforuk, Agnieszka Potasiewicz, Tomasz Kos, Piotr Popik
The combination of memantine and acetylcholinesterase inhibitors (AChEIs) is used as a therapeutic strategy to improve cognition in Alzheimer's disease. Among AChEIs, galantamine, which is also a positive allosteric modulator (PAM) of nicotinic acetylcholine receptors (nAChRs), including α7-nAChRs, may be particularly beneficial. The α7-nAChR is involved in interactions between the cholinergic and glutamatergic systems. In the present study, we investigated the potential role of α7-nAChRs in the pro-cognitive effects of this drug combination...
October 15, 2016: Behavioural Brain Research
Yun Zhai, Toru Yamashita, Yumiko Nakano, Zhuoran Sun, Jingwei Shang, Tian Feng, Ryuta Morihara, Yusuke Fukui, Yasuyuki Ohta, Nozomi Hishikawa, Koji Abe
Recently, aging societies have been showing an increasingly strong relationship between Alzheimer's disease (AD) and chronic cerebral hypoperfusion (HP). In the present study, we created a new mouse model for AD with HP, and investigated its clinical and pathological characteristics. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral HP. In contrast to simple APP23 mice, cerebral HP exacerbated motor and cognitive dysfunctions with white matter lesions and meningo-parenchymal amyloid-β (Aβ) burdens...
June 13, 2016: Journal of Alzheimer's Disease: JAD
Tae-Young Hwang, Inn-Sook Ahn, Seonwoo Kim, Doh Kwan Kim
OBJECTIVE: This study compares the efficacy of the cholinesterase inhibitor (ChEI) galantamine on cognition in patients with mild-to-moderate Alzheimer's dementia (AD) who were either naïve to ChEI drugs or who had failed a trial of the ChEI donepezil. METHODS: Outpatients with AD were sequentially referred for screening and enrollment. Current outpatients who had taken donepezil for at least 6 months without demonstrated efficacy on cognition were switched to galantamine (switched group)...
May 2016: Psychiatry Investigation
Patrícia Bacalhau, Amor A San Juan, Carolina S Marques, Daniela Peixoto, Albertino Goth, Cátia Guarda, Mara Silva, Sílvia Arantes, A Teresa Caldeira, Rosário Martins, Anthony J Burke
A library of isoquinolinone and azepanone derivatives were screened for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. The strategy adopted included (a) in vitro biological assays, against eel AChE (EeAChE) and equine serum BuChE (EqBuChE) in order to determine the compounds IC50 and their dose-response activity, consolidated by (b) molecular docking studies to evaluate the docking poses and interatomic interactions in the case of the hit compounds, validated by STD-NMR studies...
August 2016: Bioorganic Chemistry
Cindy Eckart, Agata Woźniak-Kwaśniewska, Nora A Herweg, Lluis Fuentemilla, Nico Bunzeck
Working memory (WM) can be defined as the ability to maintain and process physically absent information for a short period of time. This vital cognitive function has been related to cholinergic neuromodulation and, in independent work, to theta (4-8Hz) and alpha (9-14Hz) band oscillations. However, the relationship between both aspects remains unclear. To fill this apparent gap, we used electroencephalography (EEG) and a within-subject design in healthy humans who either received the acetylcholinesterase inhibitor galantamine (8mg) or a placebo before they performed a Sternberg WM paradigm...
August 15, 2016: NeuroImage
Julie Deguil, Laura Ravasi, Laura Lanteaume, Yves Lamberty, Regis Bordet
Empirical evidence currently supports the idea that neurovascular dysfunction is involved in the neurodegenerative process of Alzheimer's disease (AD). In fact, epidemiological studies report that i) vascular risk factors are directly associated with an increased incidence of AD and ii) vascular lesions are frequently co-existent with AD. The neurovascular unit is a key control system for oxygen and nutrients exchange between neurons and microvessels so the integrity of this system is essential for neuronal activity and cell survival...
2016: CNS & Neurological Disorders Drug Targets
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"