Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioral disturbances. Alzheimer's disease affects 15 million people worldwide and it has been estimated that Alzheimer's disease affects 4.5 million Americans. Rivastigmine is a reversible cholinesterase inhibitor used for the treatment of Alzheimer's disease. Central nervous system drug efficacy depends upon the ability of a drug to cross the blood-brain barrier and reach therapeutic concentrations in brain following systemic administration. The clinical failures of most of the potentially effective therapeutics to treat the central nervous system disorders are often not due to a lack of drug potency but rather shortcomings in the method by which the drug is delivered. Hence, considering the importance of treating Alzheimer's disease, we made an attempt to target the anti-Alzheimer's drug rivastigmine in the brain by using poly(n-butylcyanoacrylate) nanoparticles. The drug was administered as a free drug, bound to nanoparticles and also bound to nanoparticles coated with polysorbate 80. In the brain a significant increase in rivastigmine uptake was observed in the case of poly(n-butylcyanoacrylate) nanoparticles coated with 1% polysorbate 80 compared to the free drug. In conclusion that the present study demonstrates that the brain concentration of intravenously injected rivastigmine can be enhanced over 3.82 fold by binding to poly(n-butylcyanoacrylate) nanoparticles coated with 1% nonionic surfactant polysorbate 80.
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PMID:Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer's disease. 1829 51

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and functional abilities associated with various behavioral disturbances. Its impact on public health and society as a whole is devastating. Slowing of the cognitive impairment, and improvements in disease duration, self-sufficiency and behavioral disturbances represent the best outcomes of pharmacologic therapy. Cholinesterase inhibitors (ChE-I) have been shown to be effective in treating the cognitive, behavioral, and functional deficits of AD. Rivastigmine is a dual inhibitor of both acetylcholine esterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in the hydrolysis of acetylcholine. Although this drug has been shown to be beneficial in patients with AD, its benefits are limited and their long-term effectiveness has not been well demonstrated.
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PMID:Rivastigmine in Alzheimer's disease: Cognitive function and quality of life. 1851 65

Progressive deterioration in cognitive function and the ability to perform activities of daily living are the hallmarks of Alzheimer's disease (AD). As the disease progresses and behavioural/neuropsychiatric symptoms become more predominant, carers of AD patients themselves encounter a raft of physical, emotional, social and financial problems. Appropriate therapeutic management of AD patients, particularly their behavioural symptoms, may reduce the burden placed on family and professional caregivers. Preservation of cholinergic neurotransmission by cholinesterase inhibitors is the mainstay of pharmacological therapy for AD. Rivastigmine, a dual inhibitor of acetylcholinesterase and butyrylcholinesterase, has pharmacological properties that appear particularly favourable regarding the behavioural symptoms of AD. In addition to its beneficial effects on cognitive and global function, rivastigmine treatment in mild-to-moderate AD is associated with improvements in behavioural symptoms, a decreased requirement for antipsychotic drugs and delays in nursing home placement; reductions in caregiver burden, caregiver time and costs have also been reported. Rivastigmine treatment has also demonstrated improvements in behavioural symptoms and reductions in psychotropic medication usage in nursing home residents with moderate-to-severe AD, and may be associated with a reduction in professional caregiver burden. In summary, the positive effects of rivastigmine on functional and behavioural symptoms of AD help to reduce the time, stress and overall burden associated with caregiving, both in the informal home care and nursing home environments.
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PMID:Impact of rivastigmine on caregiver burden associated with Alzheimer's disease in both informal care and nursing home settings. 1858 46

Dementia associated with Parkinson's disease (PD) ultimately develops in approximately 70% of patients with PD older than 80 years of age. The neuropathology of PD dementia (PDD) is likely multifactorial and affects several neuronal populations. There is evidence that PDD is associated with a cholinergic deficit, supporting the therapeutic role of cholinesterase inhibitors, which are already first-line agents in the treatment of Alzheimer's disease. Open-label and small controlled studies suggested a clinical efficacy of cholinesterase inhibitors in PDD. One large randomized placebo-controlled trial of 541 patients demonstrated that oral rivastigmine improved cognition, attention and executive functions, activities of daily living and behavioral symptoms after 6 months of treatment. Rivastigmine is a dual cholinesterase inhibitor, being effective on both acetylcholinesterase and butyrylcholinesterase. This paper reviews the pharmacokinetic and pharmacodynamic properties of rivastigmine (oral and transdermal administration). It also reviews evidence on clinical efficacy, safety and tolerability of the oral administration in PDD patients at doses of 3-12 mg/day.
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PMID:Rivastigmine in Parkinson's disease dementia. 1867 61

Several factors are believed to give rise to the late onset sporadic form of Alzheimer's disease (LOAD). We have studied the variation at the genes of three enzymes of the cholinergic system: acetylcholinesterase, butyrylcholinesterase, and choline acetyltransferase. The single nucleotide polymorphisms (SNPs) examined were: AChE rs2571598, BChE rs1355534, BChE rs1803274, and ChAT rs2177369. The sample for the case-control study was 471 LOAD patients aged 60 years or older, and 254 subjects with no neurodegenerative disorders as the control group. A significant difference in the genotype distribution between patients and controls was observed only for ChAT rs2177369, showing that the G/G genotype was to be considered a risk factor with respect to the G/A + A/A genotypes (odds ratio = 1.56; 95% Confidence Interval = 1.10-2.22; P = 0.01). Though indicating a significant association with AD onset, our results are far from definitive since contrast with the ones reported by other authors in a previous case-control study, and call for further investigations. Among patients, 171 took part in an observational study concerning the possible role of the genetic composition on the efficacy of treatment with Donepezil and Rivastigmine. We related the SNPs of the above cited genes with cognitive status measured by MMSE. Carrying an allele or a genotype of these SNPs does not seem to play a relevant role in the response to treatment with the two cholinesterase inhibitors, though some significant results were found associated with the AChE A/A genotype that had the best response when treated with Rivastigmine.
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PMID:Variability of AChE, BChE, and ChAT genes in the late-onset form of Alzheimer's disease and relationships with response to treatment with Donepezil and Rivastigmine. 1878 Mar 1

Parkinson's disease (PD) afflicts millions of people worldwide and leads to cognitive impairment or dementia in the majority of patients over time. Parkinson's disease dementia (PDD) is characterized by deficits in attention, executive and visuospatial function, and memory. The clinical diagnostic criteria and neuropathology surrounding PDD remain controversial with evidence of overlap among PDD, dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Cortical cholinergic deficits are greater in PDD than in AD, and are well-correlated with the cognitive and neuropsychiatric dysfunction that occurs in PDD. Inhibition of acetylcholine metabolism is therefore a practical therapeutic strategy in PDD.This review examines current evidence for rivastigmine (a cholinesterase/butyrylcholinesterase inhibitor) treatment in PDD. In addition to its efficacy, we examine the safety profile, side effects, and cost effectiveness of rivastigmine in PDD. Rivastigmine provides modest benefit in PDD and further long-term studies are needed to determine the effectiveness and safety of rivastigmine over time. Tolerability is a problem for many PDD patients treated with rivastigmine. Future studies of rivastigmine in PDD should focus on pragmatic outcomes such as time to need for nursing home placement, pharmacoeconomic outcomes and simultaneous patient/caregiver quality of life assessments.
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PMID:Rivastigmine for the treatment of dementia associated with Parkinson's disease. 1930 Jun 13

3-Nitropropionic acid inhibits succinate dehydrogenase, complex II enzyme in the mitochondrial respiratory chain that leads to cellular energy deficit and oxidative stress. Huntington's disease is characterized by abnormal body movements (chorea) and cognitive dysfunctions. Rivastigmine, a well known cholinesterase inhibitor used in the management of Alzheimer's disease in a clinical practice. Recent clinical studies suggest the potential role of rivastigmine in the management of Huntington's disease. The present study has been designed to explore the possible role of rivastigmine against 3-nitropropionic acid induced behavioral, biochemical and cellular alterations. Intraperitoneal administration of 3-nitropropionic acid (10 mg/kg for 14 days) caused significant loss in body weight, motor in coordination (locomotor activity and rota rod performance) and poor memory retention in Morris water maze and elevated plus maze performance tasks as compared to vehicle treated animals. Biochemical analysis revealed significant increase in lipid peroxidation, nitrite concentration and depleted superoxide dismutase, catalase levels and alterations in mitochondrial complex enzymes (I, II, IV and MTT assay) in the different regions (striatum, cortex and hippocampus) of rat brain. Rivastigmine (0.5, 1 and 2 mg/kg, orally) once daily treatment for a period of 14 days significantly improved motor performance and cognitive task in both Morris water maze and elevated plus maze tests. Further, rivastigmine treatment significantly attenuated oxidative damage and improved mitochondrial complexes enzyme activities in different regions (striatum, cortex and hippocampus) of rat brain. The results show that rivastigmine could be used as an effective therapeutic agent in the management of Huntington's disease and related conditions.
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PMID:Protective effect of rivastigmine against 3-nitropropionic acid-induced Huntington's disease like symptoms: possible behavioural, biochemical and cellular alterations. 1944 28

Some experimental models suggest that the use of pralidoxime in carbamate toxicity is deleterious. Although pretreatment with atropine minimizes the adverse effect of pralidoxime reported in these models, concerns over the risks of pralidoxime in humans with carbamate poisoning continue. We present a unique case of carbamate toxicity treated successfully with pralidoxime alone. An 80-year-old woman with Alzheimer's dementia presented to the emergency department with 3-4 days of lightheadedness, vomiting, diarrhea, and bilateral lower extremity muscle pain. Extensive review of systems was otherwise negative. Her vital signs were BP, 207/85 mmHg; pulse, 101 beats/min; rectal temperature, 36.6( degrees )C; respirations, 18/min; and SpO(2), 95% breathing room air. Her bedside glucose measurement was 6.7 mmol/L. Physical examination revealed a confused, diaphoretic, ill-appearing woman with miosis and fasciculations of the tongue, eyelids, gastrocnemius and quadriceps bilaterally. The heart, lung, abdominal and head, eyes, ears, nose and throat examinations were otherwise unremarkable. Nine 5-cm(2) rivastigmine patches (9.5 mg/24-hour) were found adherent to her torso and lower extremities. The patches were immediately removed and underlying skin cleansed with soap and water. Laboratory values including complete blood count, basic metabolic panel, calcium, magnesium, phosphorus, troponin, coagulation studies and urinalysis were unremarkable. Due to the absence of pulmonary muscarinic findings, no atropine was administered. However, 1 g of pralidoxime was administered intravenously over 30 min to treat fasciculations. Within 30 min of this treatment, there was significant improvement in symptoms and resolution of fasciculations. She was admitted to the hospital, required no further pralidoxime therapy and was discharged after 3 days. Rivastigmine is a reversible (carbamate) cholinesterase inhibitor used to treat dementia. In overdose, cholinergic crisis is expected and in this case was precipitated by patch overuse. We believe there was a causal relationship between pralidoxime administration and the prompt resolution of symptoms and fasciculations. This case of apparently safe and effective pralidoxime use without concomitant atropine administration in a patient with carbamate toxicity reinforces recent data demonstrating the potential safety of pralidoxime in carbamate toxicity.
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PMID:Use of pralidoxime without atropine in rivastigmine (carbamate) toxicity. 1975 37

Rivastigmine is a potent acetyl- and butyrylcholinesterase inhibitor widely used for cognitive improvement in Alzheimer's disease (AD) therapy. However, dose-limiting adverse effects restrict its tolerability and clinical outcomes. This study explored new combined therapy, in which peripheral cholinergic adverse effects and central cognitive amelioration of rivastigmine were differentiated by a peripheral cholinoceptor antagonist anisodamine. The results demonstrated that rivastigmine (0.75 and 2.0 mg/kg) could significantly reverse the scopolamine-induced cognitive deficit in mice through passive avoidance test. Nevertheless, a high dose of rivastigmine (3.25 mg/kg) would compromise cognitive amelioration and produce obvious adverse effects, including hypersalivation, intestinal hyperperistalsis and muscle cramp. Interestingly, concomitant administration of anisodamine (10 mg/kg) effectively counteracted both the muscarinergic and nicotinergic adverse effects, while facilitating cognitive amelioration of rivastigmine (3.25 mg/kg). These findings provide an insight into the feasibility of combined therapy with cholinesterase inhibitors and peripheral cholinoceptor antagonists for the treatment of AD.
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PMID:Peripheral cholinoceptor antagonist anisodamine counteracts cholinergic adverse effects and facilitates cognitive amelioration of rivastigmine. 1975 70

Transportations of rivastigmine containing liposomes across Caco-2 cells were studied and in vitro test results were compared with in vivo results. MTT test was used for cell viability studies. Series of formulations were prepared containing rivastigmine which is used for the treatment of Alzheimer's disease. Characterization and stability studies for liposome formulations were performed. Encapsulation efficiencies of liposomes were 35.4%, 25.2% and 29.9% for rivastigmine, rivastigmine-sodium taurocholate, rivastigmine-dimethyl-beta-CD liposomes, respectively. In stability studies, particle size and size distribution, zeta potential, rivastigmine amounts were determined and shelf lives of liposomes were calculated. Penetration properties of rivastigmine through Caco-2 cells, dialysis membrane and kinetics of release from liposomes were determined. Permeability coefficients were calculated after diffusion studies. The highest value of % cumulative amount of rivastigmine passed through caco-2 cell cultures was found to be 87.2% for rivastigmine-sodium taurocholate solution and 12.8% for rivastigmine-sodium taurocholate liposome. The highest permeability coefficient value was obtained with sodium taurocholate liposomes for -0.75. Rivastigmine liposomes and solutions were also applied to animals. Acetyl choline esterase (AChE) activity was determined by the Ellman method on mice. %AChE inhibition values were calculated using blood and brain tissue samples. The physical appearances of the brains were investigated by TEM microscope. The highest value of AChE inhibition was observed for rivastigmine and sodium taurocholate liposomes. The histological investigations and observations also supported these results.
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PMID:Investigation of liposome formulation effects on rivastigmine transport through human colonic adenocarcinoma cell line (CACO-2). 2018 76


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