Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

Abstract

Background: Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective: The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods: Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.

Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure–activity relationships

“…The use of antioxidants may slow the progress of Alzheimer's disease (AD) and minimise neuronal degeneration (Atta-ur-Rahman & Choudhary 2001) by inhibiting acetylcholinesterase enzyme. Since the only valid hypothesis being accepted is the lack or deficiency of acetylcholine (Grossberg 2003), acetylcholinesterase inhibitors are used to treat Alzheimer's disease (Scalbert et al 2005). However, most of these drugs have side effects such as liver damage and bradycardia (Dökmeci 2000).…”

Antioxidant, anti-cholinesterase and antibacterial activities of the bark extracts of Garcinia hombroniana

“…Alzheimer Disease (AD) is a chronic and progressive neurodegenerative disorder of the brain which is characterized clinically by deterioration in activities of daily living, behaviours and cognition (Grossberg, 2003). According to the cholinergic hypothesis, memory impairment in patients suffering from AD resulted from decreased level of neurotransmitter acetylcholine.…”

A doença de Alzheimer: aspectos fisiopatológicos e farmacológicos

“…Os inibidores da acetilcolinesterase (tacrina, rivastigmina, donepezil, galantamina) alteram a função colinérgica central ao inibir as enzimas que degradam a acetilcolina (enzimas acetilcolinesterase e butirilcolinesterase), aumentando, assim, a capacidade da acetilcolina de estimular os receptores nicotínicos e muscarínicos cerebrais 60 . Desde a introdução desses medicamentos na prática clínica, os inibidores da AChE constituem o tratamento sintomático de escolha para a doença de Alzheimer 60 .…”

“…A rivastigmina (Exelon ® ), atualmente um dos medicamentos mais utilizados no tratamento da doença de Alzheimer, foi capaz de inibir tanto a enzima acetilcolinesterase quanto a butirilcolinesterase, apresentando, assim, maior eficácia quanto ao aumento dos níveis cerebrais de acetilcolina 60 . Entretanto, esse medicamento causou vários efeitos colinérgicos adversos quando a dose foi elevada abruptamente 60 .…”

“…Entretanto, esse medicamento causou vários efeitos colinérgicos adversos quando a dose foi elevada abruptamente 60 . Mais ainda, esse medicamento apresentou efeitos gastrointestinais adversos, associados ao aumento de peso 60 .…”