The Efficacy and Safety of Donepezil in Patients with Alzheimer's Disease: Results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial

Rogers, Sherise C.; Friedhoff, Lawrence

doi:10.1159/000106895

Cited by 450 publications

(414 citation statements)

References 14 publications

Supporting

Mentioning

385

Contrasting

Unclassified

Order By: Relevance

“…In phases II and III controlled trials with AD patients, the cholinesterase inhibitor donepezil significantly improved cognitive function, as measured with the AD Assessment Scale-Cognitive subscale and the Mini-Mental State Examination, MMSE, and global clinical assessment of change compared with placebo (Rogers, 1998;Rogers et al, 1998;Rogers and Friedhoff, 1996). A study of donepezil by Ogura et al (2000) achieved effects on water maze performance similar to the nicotine effects described in the studies by Levin et al: donepezil significantly decreased errors in the radial maze in rats with central cholinergic deficits.…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Mumenthaler

Yesavage

Taylor

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine) ¼ 0.80; ES (donepezil) ¼ 1.02; ES (alcohol acute) ¼ À3.66; ES (alcohol 8 h) ¼ À0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

show abstract

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Mumenthaler

Yesavage

Taylor

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…In a multicentre double-blind placebo-controlled R C T, Rogers et al 11 examined the safety and efficacy of 1, 3 or 5 mg of donepezil compared to placebo for 12 weeks in 161 outpatients with a diagnosis of probable AD. The subjects had a Mini-Mental State Examination (MMSE) score between 10 and 26, a mean age of about 71 years and no significant medical illness.…”

Section: Donepezilmentioning

confidence: 99%

The Use of Medications for Cognitive Enhancement

Pryse-Phillips

Sternberg

Rochon

et al. 2001

Can. J. Neurol. Sci.

View full text Add to dashboard Cite

Objective:To provide Canadian physicians and allied health care professionals with the evidence they need to help them make treatment decisions in the management of patients with Alzheimer’s disease or other dementias.Options:The full range and quality of diagnostic and therapeutic modalities available to Canadian physicians for the management of dementia.Outcomes:Improvement in the treatment of dementias, leading to reduced suffering, increased functional capacity and decreased economic burden.Evidence and values:The creation of these evidence-based consensus statements involved literature reviews of the subject by the authors; comparison of alternative clinical pathways and description of the methods whereby published data were analyzed; definition of the level of evidence for data in each case; evaluation and revision in a conference setting (involving primary care physicians, neurologists, psychiatrists, geriatricians, psychologists, consumers and other interested parties); insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all authors.Benefits, harms, and costs:A rational plan for the therapy of dementias is likely to lead to substantial benefits in both human and economic terms.Recommendations:Treatment decisions should be made taking into account the severity or stage of the disease, the availability of caregivers, the presence of disease affecting other bodily systems and the ability of the subject to pay the cost of the medications. Donepezil is considered to have positive effects upon certain tests of neuropsychological function and may produce some improvement in Alzheimer’s disease of mild to moderate severity as measured by rating scales. Its ability to improve quality of life remains uncertain. No other drug treatments* (apart from symptomatic therapies) are at present approved for the treatment of Alzheimer’s disease.Validation:These recommendations were created by a writing committee, evaluated and revised at a consensus conference and further reviewed and revised by the writing committee prior to publication.

show abstract

“…Besides the strong interacting abilities of Donepezil, its administration as drug was also associated with several undesirable effects [37,38]. The observed undesirable effects associated with administration of various hAChE inhibitors initiated the quest for the design of specific and potent hAChE inhibitors, which can precisely interact with residues of PAS and also can span the gorge so as Donepezil.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in silico evaluation of 1N-methyl-1S-methyl-2-nitroethylene (NMSM) derivatives against Alzheimer disease: to understand their interacting mechanism with acetylcholinesterase

et al. 2012

View full text Add to dashboard Cite

Anomalous action of human acetylcholinesterase (hAChE) in Alzheimer's disease (AD) was restrained by various AChE inhibitors, of which the specific and potent lead candidate Donepezil is used for treating the disease AD. Besides the specificity, the observed undesirable side effects caused by Donepezil invoked the quest for new lead molecules with the increased potency and specificity for AChE. The present study elucidates the potency of six 1N-methyl-1S-methyl-2-nitroethylene (NMSM) derivatives to form a specific interaction with the peripheral anionic site and catalytic anionic subsite residues of hAChE. The NMSMs were prepared in good yield from 1,1-di(methylsulfanyl)-2-nitroethylene and primary amine (or) amino acid esters. In silico interaction analysis reveals specific and potent interactions between hAChE and selected ligand molecules. The sitespecific interactions formed between these molecules also results in a conformational change in the orientation of active site residues of hAChE, which prevents them from being accessed by beta-amyloid protein (Aβ), which is a causative agent for amyloid plaque formation and acetylcholine (ACh). In silico interaction analysis between the ligand-bounded hAChE with Aß and ACh confirms this observation. The variation in the conformation of hAChE associated with the decreased ability of Aβ and ACh to access the respective functional residues of hAChE induced by the novel NMSMs favors their selection for in vivo analysis to present themselves as new members of hAChE inhibitors.

show abstract

The Efficacy and Safety of Donepezil in Patients with Alzheimer's Disease: Results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial

Cited by 450 publications

References 14 publications

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

The Use of Medications for Cognitive Enhancement

Synthesis and in silico evaluation of 1N-methyl-1S-methyl-2-nitroethylene (NMSM) derivatives against Alzheimer disease: to understand their interacting mechanism with acetylcholinesterase

Contact Info

Product

Resources

About