A Systematic Review on Donepezil-based Derivatives as Potential Cholinesterase Inhibitors for Alzheimer's Disease

Curr Med Chem. 2019;26(30):5625-5648. doi: 10.2174/0929867325666180517094023.

Abstract

Alzheimer's Disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also through reduction of β-amyloid burden. This review presents the overview of donepezilrelated compounds as potential anti-AD drugs developed on the basis of cholinergic hypothesis to act as solely AChE and butyrylcholinesterase (BChE) inhibitors.

Keywords: Alzheimer’s disease; NMDA; acetylcholinesterase; butyrylcholinesterase; donepezil; inhibitor; treatment..

Publication types

  • Systematic Review

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Inhibitors / therapeutic use*
  • Donepezil / chemistry
  • Donepezil / pharmacology*
  • Donepezil / therapeutic use*
  • Humans
  • Molecular Structure
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use*

Substances

  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Donepezil
  • Acetylcholinesterase
  • Butyrylcholinesterase