Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease

Abstract

ABSTRACT:We reviewed the literature on the pharmacological characteristics and role of donepezil in Alzheimer disease. We performed an evidence-based review of randomized controlled trials by searching sources such as PubMed, MEDLINE, Google Scholar, and Clinical Key. In total, 18 randomized clinical trials were identified. In amnestic mild cognitive impairment (MCI), data showed that donepezil delays progression to Alzheimer disease. However, for mild-to-moderate and moderate-to-severe Alzheimer disease, it proved effective in slowing cognitive and global function decline. Discontinuation of donepezil results in acceleration of disease progression. The effects of donepezil on behavioral symptoms have shown mixed outcomes. Donepezil is the standard of care in Alzheimer disease as it is well tolerated and has self-limiting gastrointestinal adverse effects. In amnestic MCI, off-label use of donepezil can be considered after risk stratification of conversion to Alzheimer disease.

Memantine and Its Combination with Acetylcholinesterase Inhibitors in Pharmacological Pretreatment of Soman Poisoning in Mice

“…Among them, the combination with donepezil gave the best results (protective ratio of 5.12). The explanation may relate to its pharmacodynamic properties: donepezil acts rapidly as reversible, mixed competitive, and non-competitive selective AChEI; the AChE/BChE ratio in humans is 405:1 (Zeb et al 2017). Donepezil interacts with both the catalytic and peripheral binding sites, resulting in enhanced AChE inhibition (Cheung et al 2012).…”

Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease

“…The mechanisms by which AChE inhibitors block the catalytic action of the enzyme fall into three major categories: competitive inhibition, pseudo-irreversible inhibitions, and irreversible inhibition [ 10 ]. Donepezil is a selective, noncompetitive, and rapidly reversible inhibitor [ 11 ]; galanthamine acts as a reversible and competitive acetylcholinesterase inhibitor that also up-regulates the expression of nicotinic receptors [ 12 ]; rivastigmine is pseudo-irreversible and also inhibits BChE [ 7 , 13 ]. Tacrine, the first reversible dual AChE and BChE inhibitor used in AD therapy, has been withdrawn from the market due to its hepatotoxicity [ 14 ].…”

Docking molecular, síntese e estudo biológico de potenciais inibidores da beta-secretase (BACE-1) e da acetilcolinesterase (AChE)

“…A donepezila e galantamina inibem a AChE e a rivastigmina inibe a AChE e a BChE (butirilcolinesterase). Apesar de existirem estudos descrevendo a ação da donepezila59 e da rivastigmina57 em todos estágios da DA, comumente donepezila, rivastigmina e galantamina são fármacos indicados para DA de leve a moderada 60 e a memantina para os estágios moderado a severo61 . Esses fármacos se diferenciam em termos de características farmacológicas e meios de administração.…”