ドネペジル

A: Donepezil is a potent and selective inhibitor of acetylcholinesterase (AChE) [, , , ]. AChE is an enzyme that breaks down the neurotransmitter acetylcholine (ACh) in the synaptic cleft. By inhibiting AChE, donepezil increases the concentration of ACh in the synapse, thereby enhancing cholinergic neurotransmission [, ]. This effect is thought to be the primary mechanism by which donepezil exerts its therapeutic effects in Alzheimer's disease (AD), as AD is characterized by a decline in cholinergic function [, , ].

ANone: While this information is readily available in chemical databases and the literature, the current scientific articles provided do not delve into the specific spectroscopic properties of donepezil.

A: Studies have shown that donepezil exhibits stability in various formulations, including oral tablets and transdermal patches [, , ]. Research focusing on the transdermal delivery system (TDS) demonstrates its ability to release donepezil consistently over a period of 72 hours in healthy volunteers []. Notably, the average donepezil residue in the TDS after this period remained high, ranging from approximately 73.9% to 86.7% of the initial loading dose []. This suggests sustained release and stability of donepezil within the TDS matrix.

A: Donepezil acts as an enzyme inhibitor, not a catalyst. It binds to AChE and prevents it from breaking down ACh [, , , ].

ANone: While computational studies are essential in drug discovery, the provided articles do not extensively discuss computational chemistry investigations regarding donepezil.

ANone: While SAR studies are crucial for drug development, the provided articles focus primarily on the clinical effects of donepezil rather than exploring SAR.

A: Donepezil has been formulated for both oral and transdermal delivery, indicating its stability in various pharmaceutical forms [, , ]. Notably, a donepezil transdermal patch has been developed and studied [, , ]. This patch has been shown to deliver donepezil consistently over a 72-hour period, with a high percentage of the drug remaining in the patch after use []. This suggests good stability of donepezil within the patch formulation.

A: Donepezil has shown efficacy in preclinical models and clinical trials for AD [, , , , , , , , , , , ]. In animal models, donepezil has been shown to improve cognitive function and reduce amyloid-beta (Aβ) aggregation, a hallmark of AD [, , ]. Clinical trials have demonstrated that donepezil provides statistically significant, albeit modest, improvements in cognitive function and global function in patients with mild to moderate AD [, , , , , , , , ].

A: While some patients may experience a waning of response to donepezil over time, this is not typically considered to be due to the development of classical drug resistance as seen with antibiotics [, ]. The progressive nature of AD itself is the likely reason for the eventual decline in cognitive function despite treatment [, ].

A: Donepezil is generally well-tolerated, with the most common adverse effects being gastrointestinal in nature, such as nausea, vomiting, and diarrhea [, , , , ]. These side effects are usually mild and transient, often resolving with continued treatment or dose adjustment [, , , , ].

A: The development of the transdermal donepezil patch represents a significant step towards enhancing its delivery profile [, , ]. This delivery route bypasses first-pass metabolism in the liver and potentially offers more consistent drug levels, potentially minimizing side effects [, ].

ANone: While biomarkers for AD diagnosis and progression are constantly being investigated, the use of specific biomarkers to predict or monitor donepezil response remains an active area of research.

A: Research on donepezil employs various analytical techniques, with a particular emphasis on accurately measuring donepezil concentrations in biological samples like plasma [, ]. This is often achieved using highly sensitive and specific methods like liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) [, ]. This technique enables researchers to quantify even minute amounts of donepezil, which is essential for understanding its pharmacokinetic profile and ensuring appropriate dosage regimens.

ANone: As with many pharmaceuticals, understanding the environmental fate and potential impact of donepezil requires further investigation.

A: Oral donepezil formulations typically exhibit good dissolution and absorption, contributing to its high bioavailability [, ]. The development of transdermal patches aims to further optimize drug delivery and potentially reduce fluctuations in plasma levels [, , ].

A: The use of validated analytical methods is paramount in ensuring accurate and reliable data in donepezil research []. Validation involves rigorous assessments of various parameters including accuracy, precision, specificity, linearity, range, detection limit, quantitation limit, robustness, and system suitability []. By adhering to these stringent standards, researchers can confidently analyze donepezil concentrations in biological samples, facilitating meaningful interpretations of pharmacokinetic and pharmacodynamic data.

A: The production and distribution of donepezil are subject to strict quality control measures throughout the entire process, from development and manufacturing to distribution. These measures ensure the drug's safety, efficacy, and consistency [, ].

A: Donepezil is generally well-tolerated, and significant immune reactions are not commonly reported [, , , , ].

ANone: While donepezil is primarily metabolized by liver enzymes, information regarding specific interactions with drug transporters is limited in the provided research.

A: Donepezil is primarily metabolized by CYP2D6 and CYP3A4 enzymes in the liver [, , ]. Co-administration with drugs that inhibit these enzymes could potentially increase donepezil levels, necessitating dosage adjustments to avoid adverse effects [, , ].

ANone: As with many pharmaceuticals, proper disposal of unused medication and pharmaceutical waste is essential to minimize environmental impact. Specific guidelines may vary depending on local regulations.

A: Research in this field benefits from access to various resources including preclinical models, clinical trial networks, brain imaging facilities, and biological sample repositories [, , , , , , , , ].

A: The approval of donepezil in 1996 marked a significant advancement in the treatment of AD [, , ]. The subsequent development of the transdermal patch formulation further improved treatment options by offering an alternative delivery route with potentially improved adherence and reduced side effects [, , , ].

A: The development and investigation of donepezil exemplify successful cross-disciplinary collaborations, involving researchers from diverse fields such as neuroscience, pharmacology, medicinal chemistry, and clinical medicine []. These collaborations have been instrumental in understanding the mechanism of action, pharmacokinetics, efficacy, and safety of donepezil, ultimately leading to improved treatment options for AD patients [].