Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this study was to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effect on delirium in vascular dementia (VaD). The results from this follow-up study suggest that although delirium is frequent in elderly, cognitively impaired patients, it might not be a simple consequence of acute disease and hospitalization. Rather, delirium can be secondary to brain damage and to metabolic disturbances. According to the Lewy body dementia model, delirium could be induced by a lack of acetylcholine in the brain. Rivastigmine may help reduce the frequency of delirium episodes and help shorten their duration. Additional studies are required to better define the causes of delirium, which currently has no definitive treatment.
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PMID:Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24-month study of 246 patients. 1563 41

An isocratic, reversed-phase liquid chromatographic (RPLC) method was developed for the quantitative determination of Rivastigmine hydrogen tartrate, a cholinesterase inhibitor in bulk drugs and in pharmaceutical dosage forms. The developed method is also applicable for the related substance determination of Rivastigmine hydrogen tartrate in bulk drugs. The chromatographic separation was achieved on a Waters X Terra RP18 (250 mm x 4.6 mm, 5 microm) column using aqueous 0.01 M sodium-1-heptane sulphonate (pH: 3.0 with dilute phosphoric acid)-acetonitrile (72:28, v/v) as a mobile phase. The chromatographic resolution between Rivastigmine and its potential impurity, namely (S)-3-(1-dimethylaminoethyl) phenol (Imp 1) was found to be greater than four. Forced degradation studies were performed for Rivastigmine hydrogen tartrate bulk drug using acid (0.5 N hydrochloric acid), base (0.5 N sodium hydroxide), oxidation (3% hydrogen peroxide), heat (60 degrees C) and UV light (254 nm). No degradation was observed for Rivastigmine hydrogen tartrate except in base hydrolysis and the formed degradation product was found to be Imp 1. The mass balance of Rivastigmine hydrogen tartrate was close to 100 in all the stress conditions. The limit of detection (LOD) and limit of quantification (LOQ) of Imp 1 were found to be 100 and 300 ng/ml, respectively, for 10 microl injection volume. The percentage recovery of Imp 1 in bulk drug sample was ranged from 95.2 to 104.3. The active pharmaceutical ingredient was extracted from its finished dosage form (capsule) using water. The percentage recovery of Rivastigmine hydrogen tartrate was ranged from 99.2 to 101.3 and 98.6 to 101.5 in bulk and pharmaceutical formulation samples, respectively. Rivastigmine hydrogen tartrate sample solution and mobile phase were found to be stable for at least 48 h. The developed method was validated with respect to linearity, accuracy, precision, robustness and forced degradation studies prove the stability indicating power of the method.
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PMID:A stability indicating LC method for rivastigmine hydrogen tartrate. 1566 43

This analysis aimed to assess mini-mental state examination (MMSE) scores in patients with Alzheimer's disease who received rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, for up to 5 years. Rivastigmine data came from two pooled open-label extensions of four 6-month, randomised, placebo-controlled trials. Projections of decline, had the same patients not been treated, were made using a baseline-dependent mathematical model. MMSE data were available for 1998 rivastigmine-treated patients and 657, 298 and 83 were still on treatment at 3, 4 and 5 years, respectively. The mean (+/-SD) baseline MMSE score was 19.3 (+/-4.9). Projected mean scores in model-based untreated patients declined below 10 points on the MMSE at about 3 years, while the mean MMSE score of patients who remained on rivastigmine stayed above 10 points for 5 years.
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PMID:Cognitive performance in Alzheimer's disease patients receiving rivastigmine for up to 5 years. 1585 67

A new and accurate chiral liquid chromatographic method was developed for the enantiomeric resolution of Rivastigmine hydrogen tartarate, (-)S-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methylphenyl-carbamate hydrogen tartarate, a cholinesterase inhibitor in bulk drugs. The enantiomers of Rivastigmine hydrogen tartarate were baseline resolved on a Chiralcel OD-H (250 mm x 4.6 mm, 5 microm) column using a mobile phase system containing hexane: isopropanol: trifluoroacetic acid (80:20:0.2, v/v/v). The resolution between the enantiomers was not less than four and interestingly distomer was eluted prior to eutomer in the developed method. The presence of trifluoroacetic acid in the mobile phase has played an important role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was extensively validated and proved to be robust. The limit of detection and limit of quantification of (R)-enantiomer were found to be 500 and 1500 ng/ml, respectively for 10 microl injection volume. The percentage recovery of (R)-enantiomer was ranged from 95.2 to 104.3 in bulk drug samples of Rivastigmine hydrogen tartarate. Rivastigmine hydrogen tartarate sample solution and mobile phase were found to be stable for at least 48 h. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-enantiomer in bulk drugs. Chiralcel OJ-H column can also be used as an alternative for the above purpose.
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PMID:A validated chiral liquid chromatographic method for the enantiomeric separation of Rivastigmine hydrogen tartarate, a cholinesterase inhibitor. 1592 25

Rivastigmine is a second-generation cholinesterase inhibitor with selectivity for the CNS, with capacity to inhibit both acetylcholinesterase and butyrylcholinesterase. Rivastigmine is currently approved for the treatment of mild-to-moderate Alzheimer's disease. In addition to its effects on cognition and activities of daily living, rivastigmine appears to be useful in preventing and controlling behavioral and neuropsychiatric manifestations in Alzheimer's disease and dementia with Lewy bodies. This drug profile could be potentially useful in patients with subcortical vascular dementia who often present these symptoms. Small open-label studies of patients with subcortical vascular dementia showed that rivastigmine improved attention, executive function, apathy and other behavioral deficits. Rivastigmine appears to be a promising agent in vascular dementia but its effects remain to be established in double-blind, placebo-controlled clinical trials.
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PMID:Rivastigmine for subcortical vascular dementia. 1593 63

Pharmacological therapy in Alzheimer's disease. Current clinical practice in The Netherlands. Dementia affects 195,000 patients of 65 years and older in The Netherlands currently. Rivastigmine and galantamine, both cholinesterase inhibitors, and memantine, an NMDA (N-methyl-D-aspartate) antagonist, are licensed for the treatment of AD. In clinical practice, these drugs have limited effects on cognitive and other symptoms of dementia. We describe the practical care of some patients treated with these drugs and discuss the pros and cons of pharmacotherapy in AD. Extensive knowledge of the drugs, other treatment options and of dementia are necessary for good clinical practice in the treatment of these patients and the counselling of their caregivers.
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PMID:[Pharmacological therapy in Alzheimer's disease. Current clinical practice in The Netherlands]. 1607 59

Alzheimer's disease is the most common form of neurodegenerative dementia and poses considerable health challenges to both patients and their families. Rivastigmine is a powerful slow-reversible, noncompetitive carbamate cholinesterase inhibitor that is approved for the treatment of mild-to-moderate Alzheimer's disease. Randomized, double-blind, placebo-controlled trials of up to 6 months duration have shown beneficial effects of rivastigmine compared with placebo in measures of cognition and global functioning. Less rigorous but growing data suggest that the beneficial effects may endure for up to 5 years, extend to more advanced stages of Alzheimer's disease and may occur in noncognitive domains, such as activities of daily living and the behavioral symptoms of Alzheimer's disease. Evidence from controlled studies also supports the use of rivastigmine for cognitive and behavioral symptoms in Alzheimer's disease associated with vascular risk factors, dementia with Lewy bodies and Parkinson's disease dementia. Early and continued treatment of Alzheimer's disease with rivastigmine maximizes the observed beneficial effects. The most prominent adverse effect of rivastigmine is centrally mediated cholinergic gastrointestinal events, which can be minimized by slower dose-escalation intervals and administration with a full meal. Therapeutic dosing is 6-12 mg/day given twice daily, with higher doses having the potential for greater benefits.
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PMID:Rivastigmine for Alzheimer's disease. 1616 80

Vascular dementia (VaD), like Alzheimer's disease (AD), is associated with cholinergic deficits. Rivastigmine provides sustained, brain-selective inhibition of acetylcholinesterase and butyrylcholinesterase. Preliminary data suggest that rivastigmine may provide significant benefits in patients with AD and cerebrovascular disease (mixed dementia), and in patients with VaD. Open-label rivastigmine treatment has been associated with improved cognitive and functional abilities, behavioral symptoms, and reduced caregiver stress in a small pilot study in these patients. Larger, prospective, double-blind studies of rivastigmine in patients with VaD are under way. These studies will confirm whether rivastigmine is an efficacious treatment option for a range of patients for whom, until now, there have been few symptomatic therapies.
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PMID:Rivastigmine in vascular dementia. 1619 Dec 41

Acetylcholinesterase and butyrylcholinesterase activities emerge in association with plaques and tangles in Alzheimer's disease. These pathological cholinesterases, with altered properties, are suggested to participate in formation of plaques. The present experiment assessed the ability of rivastigmine, a clinically utilized agent that inhibits acetylcholinesterase and butyrylcholinesterase activities, to inhibit cholinesterases in plaques and tangles. Cortical sections from cases of Alzheimer's disease were processed using cholinesterase histochemistry in the presence or absence of rivastigmine. Optical densities of stained sections were utilized as a measure of inhibition. The potency of rivastigmine was compared with those of other specific inhibitors. Optimum staining for cholinesterases in neurons and axons was obtained at pH 8.0. Cholinesterases in plaques, tangles and glia were stained best at pH 6.8. Butyrylcholinesterase-positive plaques were more numerous than acetylcholinesterase-positive plaques. Rivastigmine inhibited acetylcholinesterase in all positive structures in a dose-dependent manner (10(-6)-10(-4) M). However, even at the highest concentration, faint activity remained. In contrast, rivastigmine resulted in complete inhibition of butyrylcholinesterase in all structures at 10(-5) M. Rivastigmine was equipotent to the specific acetylcholinesterase inhibitor BW284C51 and more potent than the butyrylcholinesterase inhibitors iso-OMPA and ethopropazine. In conclusion, rivastigmine is a potent inhibitor of acetylcholinesterase and a more potent inhibitor of butyrylcholinesterase in plaques and tangles. Unlike other cholinesterase inhibitors tested, rivastigmine inhibited cholinesterases in normal and pathological structures with the same potency. Thus, at the therapeutic concentrations used, rivastigmine is likely to result in inhibition of pathological cholinesterases, with the potential of interfering with the disease process.
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PMID:Rivastigmine is a potent inhibitor of acetyl- and butyrylcholinesterase in Alzheimer's plaques and tangles. 1621 45

Cognitive decline is conventionally regarded as the defining clinical symptom of Alzheimer's disease (AD), but behavioral and neuropsychiatric symptoms are also present throughout the course of the disease. In fact, behavioral symptoms may appear before cognitive decline is diagnosed. The presence of these symptoms may predict an increasing need for community-based services or even nursing home placement. The characteristic behavioral and neuropsychiatric symptoms associated with AD may be related to the same pathophysiology that underlies the cognitive abnormalities. AD is characterized by a loss of cholinergic neurons as well as by the presence of neurofibrillary tangles (NFTs) and senile plaques in brain regions with cholinergic deficits, resulting in a deficiency in acetylcholine (ACh) in areas of the brain that modulate cognition, behavior, and emotion. Cholinesterase inhibitors are thought to augment or maximize the concentration of ACh in the synaptic cleft. Rivastigmine is a dual inhibitor of both acetylcholin esterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in hydrolysis of ACh. Literature searches using MEDLINE and EMBASE databases were performed to identify studies of rivastigmine (through August 2005) that assessed neuropsychiatric aspects of AD. Rivastigmine has been demonstrated to be safe and effective in stabilizing or improving the cognitive symptoms of AD in 3 large, well-controlled, randomized clinical trials, which also demonstrated that rivastig mine improves overall global functioning. Smaller studies and meta-analyses of pooled data from the 3 large trials have suggested that rivastigmine may improve the behavioral and neuropsychiatric symptoms associated with AD.
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PMID:Effect of rivastigmine in the treatment of behavioral disturbances associated with dementia: review of neuropsychiatric impairment in Alzheimer's disease. 1623 3


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