ArticleNeurochemical research2008
Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental Alzheimer therapeutic, dihydrobenzodioxepine cymserine.
Article in Neurochemical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 69 citations in OpenAlex.
- Targeting Neurodegeneration: The Emerging Role of Hybrid Drugs.Current drug targets · 2025Review
- Conjugates of Methylene Blue with Cycloalkaneindoles as New Multifunctional Agents for Potential Treatment of Neurodegenerative Disease.International journal of molecular sciences · 2022Article
- Article
- Cholinesterase inhibitory activity of tinosporide and 8-hydroxytinosporide isolated fromSaudi journal of biological sciences · 2021Article
- Carbamate group as structural motif in drugs: a review of carbamate derivatives used as therapeutic agents.Arhiv za higijenu rada i toksikologiju · 2020Review
- Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases.Scientific reports · 2019Article
- Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer's disease.Chemistry Central journal · 2018Review
- Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment.Scientific reports · 2017Article
- Inhibition of Butyrylcholinesterase with Fluorobenzylcymserine, An Experimental Alzheimer's Drug Candidate: Validation of Enzoinformatics Results by Classical and Innovative Enzyme Kinetic Analyses.CNS & neurological disorders drug targets · 2017Article
- Conjugates of γ-Carbolines and Phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer Disease.Scientific reports · 2015Article
- Linking Alzheimer's disease and type 2 diabetes mellitus via aberrant insulin signaling and inflammation.CNS & neurological disorders drug targets · 2014Review
- Inhibitory evaluation of sulfonamide chalcones on β-secretase and acylcholinesterase.Molecules (Basel, Switzerland) · 2012Article
- Determination of sugars in honey by liquid chromatography.Saudi journal of biological sciences · 2011Article
- Multiple approaches to analyse the data for rat brain acetylcholinesterase inhibition by cyclophosphamide.Neurochemical research · 2010Article
- Estimation of BTEX in groundwater by using gas chromatography-mass spectrometry.Saudi journal of biological sciences · 2010Article
- Targeting BuChE-inflammatory pathway by SK0506 to manage type 2 diabetes and Alzheimer disease.Neurochemical research · 2009Article
- Tetrahydrofurobenzofuran cymserine, a potent butyrylcholinesterase inhibitor and experimental Alzheimer drug candidate, enzyme kinetic analysis.Journal of neural transmission (Vienna, Austria : 1996) · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Cholinergic loss is the single most replicated neurotransmitter deficiency in Alzheimer's disease (AD) and has led to the use of acetylcholinesterase inhibitors (AChE-Is) and unselective cholinesterase inhibitors (ChE-Is) as the mainstay of treatment. AChE-Is and ChE-Is, however, induce dose-limiting adverse effects. Recent studies indicate that selective butyrylcholinesterase inhibitors (BuChE-Is) elevate acetylcholine (ACh) in brain, augment long-term potentiation, and improve cognitive performance in rodents without the classic adverse actions of AChE-Is and ChE-Is. BuChE-Is thereby represent a new strategy to ameliorate AD, particularly since AChE activity is depleted in AD brain, in line with ACh levels, whereas BuChE activity is elevated. Our studies have focused on the design and development of cymserine analogues to induce selective time-dependent brain BuChE inhibition, and on the application of innovative and quantitative enzyme kinetic analyses to aid selection of drug candidates. The quantitative interaction of the novel inhibitor, dihydrobenzodioxepine cymserine (DHBDC), with human BuChE was characterized. DHBDC demonstrated potent concentration-dependent binding with BuChE. The IC(50) and specific new kinetic constants, such as K(T50), P(PC), K(T1/2) and R(I), were determined at dual substrate concentrations of 0.10 and 0.60 mM butyrylthiocholine and reaction times, and are likely attainable in humans. Other classical kinetic parameters such as K(ia), K(ma), V(ma) and V(mi) were also determined. In synopsis, DHBDC proved to be a highly potent competitive inhibitor of human BuChE in comparison to its structural analogue, cymserine, and represents an interesting drug candidate for AD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.