Half-inhibition Concentrations of New Cholinesterase Inhibitors

2004 ◽  
Vol 59 (3-4) ◽  
pp. 293-296 ◽  
Author(s):  
Pavla Zdražilová ◽  
Šárka Štĕpánková ◽  
Karel Komers ◽  
Karel Ventura ◽  
Alexander Čegan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Cholinesterase Inhibitors ◽  
Molar Concentration ◽  
Disease Treatment ◽  
Hydrolysis Of

The power of chosen carbamates and hydrazinium derivatives (carbazates) to inhibit the hydrolysis of acetylthiocholine by butyrylcholinesterase or acetylcholinesterase was tested. The determined pI50 values (= negative logarithm of the molar concentration inhibiting the enzyme activity by 50%) of the tested substances were compared with pI50 values of the commercially used drugs for the Alzheimer’s disease treatment - rivastigmine and galanthamine.

Amiridine-piperazine hybrids as cholinesterase inhibitors and potential multitarget agents for Alzheimer's disease treatment

2021 ◽  
Vol 112 ◽  
pp. 104974
Author(s):  
Galina F. Makhaeva ◽  
Sofya V. Lushchekina ◽  
Nadezhda V. Kovaleva ◽  
Tatiana Yu. Astakhova ◽  
Natalia P. Boltneva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Disease Treatment

scholarly journals Inhibition of Cholinesterase by Dialkylcarbamates

2007 ◽  
Vol 62 (3-4) ◽  
pp. 308-310 ◽  
Author(s):  
Šárka Štĕpánková ◽  
Karel Komers ◽  
Alena Komersová ◽  
Markéta Masopustová ◽  
Alexander Čegan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Blood Brain Barrier ◽  
Molar Concentration ◽  
Brain Barrier ◽  
Separation Coefficient ◽  
Blood Brain

Abstract The pI50 index and separation coefficients of chosen 3-N,N-diethylaminophenyl-N′,N′-dialkylcarbamates were determined. Index pI50 (pI50 = negative logarithm of molar concentration of inhibitor inhibiting the enzyme activity by 50%) describes the effectiveness of the inhibitor. The rate of ability of the inhibitor to pass the blood-brain barrier is usually described by the separation coefficient in a system n-octanol/water (Kow). Obtained results were compared with pI50 and Kow of Exelon®, the commercially used drug against the Alzheimer’s disease.

scholarly journals Trends and disparities in the use of cholinesterase inhibitors to treat Alzheimer’s disease dispensed by the Brazilian public health system – 2008 to 2014: a nation-wide analysis

2018 ◽  
Vol 76 (7) ◽  
pp. 444-451 ◽  
Author(s):  
Flávia Silva de Moraes ◽  
Mariana Lima Cerqueira de Souza ◽  
Giancarlo Lucchetti ◽  
Alessandra Lamas Granero Lucchetti
Keyword(s):  
Public Health ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health System ◽  
Cholinesterase Inhibitors ◽  
Public Health System ◽  
Disease Treatment ◽  
Free Distribution ◽  
Unified Health System ◽  
Over Time

ABSTRACT In light of the high cost of dementia treatment, there is legislation authorizing free distribution of cholinesterase inhibitors to those suffering from Alzheimer’s disease in Brazil. However, the existence of this free distribution does not guarantee adequate distribution. Objectives The present study aimed to investigate the trends of prescriptions and the coverage of Alzheimer’s disease treatment using cholinesterase inhibitors from public pharmacies dispensing high-cost drugs in Brazil. Methods This was a retrospective study that collected data from the Brazilian public Unified Health System. All cholinesterase inhibitors distributed at no cost to Brazilians during the year 2014, as well as the estimated number and percentages of patients who used these medications, were evaluated and compared to data from the year 2008. Results Our estimates indicated that 9.7% of the population having dementia syndromes used cholinesterase inhibitors, as well as 16.1% of those with Alzheimer’s disease in Brazil. A clear disparity was noted between the use and distribution of cholinesterase inhibitors, depending on the region in which they were found. Over time, an increase in the distribution of cholinesterase inhibitors has been noted. In 2008, that use was 12.0% whereas, in 2014, it was 16.1%, an increase of 34% in six years. Conclusion It was estimated that 16.1% of patients with Alzheimer’s disease in Brazil use cholinesterase inhibitors. These values have increased and, in spite of not being satisfactory, they indicate a potential for improvement. However, there is still a significant disparity among the regions.

scholarly journals Association between human paraoxonase 2 protein and efficacy of acetylcholinesterase inhibiting drugs used against Alzheimer’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258879
Author(s):  
Fauzia Parween ◽  
Md. Summon Hossain ◽  
Kshetra Pal Singh ◽  
Rinkoo Devi Gupta
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Esterase Activity ◽  
Ache Activity ◽  
Simultaneous Occurrence ◽  
Individual Response ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Hydrolysis Of

Serum Paraoxonase 2 (PON2) level is a potential biomarker owing to its association with a number of pathophysiological conditions such as atherosclerosis and cardiovascular disease. Since cholinergic deficiency is closely linked with Alzheimer’s disease (AD) progression, acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with AD. However, there is a heterogenous response to these drugs and mostly the subjects do not respond to the treatment. Gene polymorphism, the simultaneous occurrence of two or more discontinuous alleles in a population, could be one of the important factors for this. Hence, we hypothesized that PON2 and its polymorphic forms may be hydrolyzing the AChEIs differently, and thus, different patients respond differently. To investigate this, two AChEIs, donepezil hydrochloride (DHC) and pyridostigmine bromide (PB), were selected. Human PON2 wildtype gene and four mutants, two catalytic sites, and two polymorphic sites were cloned, recombinantly expressed, and purified for in vitro analysis. Enzyme activity and AChE activity were measured to quantitate the amount of DHC and PB hydrolyzed by the wildtype and the mutant proteins. Herein, PON2 esterase activity and AChE inhibitor efficiency were found to be inversely related. A significant difference in enzyme activity of the catalytic site mutants was observed as compared to the wildtype, and subsequent AChE activity showed that esterase activity of PON2 is responsible for the hydrolysis of DHC and PB. Interestingly, PON2 polymorphic site mutants showed increased esterase activity; therefore, this could be the reason for the ineffectiveness of the drugs. Thus, our data suggested that the esterase activity of PON2 was mainly responsible for the hydrolysis of AChEI, DHC, and PB, and that might be responsible for the variation in individual response to AChEI therapy.

Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives

2019 ◽  
Vol 19 (8) ◽  
pp. 688-705
Author(s):  
Taibi Ben Hadda ◽  
Abdur Rauf ◽  
Hsaine Zgou ◽  
Fatma Sezer Senol ◽  
Ilkay Erdogan Orhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Metal Accumulation ◽  
Microtiter Plate ◽  
Metal Chelation ◽  
Carbonyl Derivatives ◽  
Cholinesterase Inhibitory Activity ◽  
Inhibitory Potential

Background:Since deficit of acetylcholine has been evidenced in the Alzheimer’s disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.Method:In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 μg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.Results and Conclusion:All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good harmonization with experimental data.

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

Huprine Y – tryptophan heterodimers with potential implication to Alzheimer’s disease treatment

2021 ◽  
pp. 128100
Author(s):  
Eva Mezeiova ◽  
Martina Hrabinova ◽  
Vendula Hepnarova ◽  
Daniel Jun ◽  
Jana Janockova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Treatment ◽  
Potential Implication
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