Cholinesterase inhibitors for Alzheimer's disease: Multitargeting strategy based on anti-Alzheimer's drugs repositioning

Md Tanvir Kabir, Md Sahab Uddin*, Mst Marium Begum, Shanmugam Thangapandiyan, Md Sohanur Rahman, Lotfi Aleya, Bijo Mathew, Muniruddin Ahmed, George E. Barreto, Ghulam Md Ashraf

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

100 Citations (Scopus)

Abstract

In the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improvement of AD. Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AChE for myasthenia gravis had effectively proven that AChE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEIs) have been continued to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs which are under development and their respective mechanisms of actions.

Original languageEnglish
Pages (from-to)3519-3535
Number of pages17
JournalCurrent Pharmaceutical Design
Volume25
Issue number33
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Acetylcholine
  • Acetylcholinesterase inhibitors
  • Alzheimer's disease
  • Donepezil
  • Galantamine
  • Rivastigmine
  • Tacrine

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