Donepezil and Memantine Derivatives for Dual-Function and Prodrug Applications in Alzheimer's Disease.

ABSTRACT: The treatment of Alzheimer's disease by acetylcholinesterase (AChE) and N-methyl-d-aspartate receptor (NMDAR) inhibitors is limited by the narrow therapeutic window and adverse side effects of the drugs. This study aims to increase the efficacy and limit the side effects of donepezil, an AChE inhibitor, and memantine, an NMDAR inhibitor, through the addition of amyloid-β (Aβ)-targeting fragments to create dual-function compounds. The incorporation of the amyloid-targeting fragments successfully produced compounds with affinity for Aβ fibrils, and that can stain amyloid plaques in the brains of 5xFAD mice. The donepezil-based compounds showed significant changes in AChE inhibition compared to donepezil due to the incorporation of the Aβ-targeting fragment and as confirmed by molecula

SUBMITTER: Terpstra K 

PROVIDER: S-EPMC12414536 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature