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- Title
Memantine Derivatives as Multitarget Agents in Alzheimer's Disease.
- Authors
Marotta, Giambattista; Basagni, Filippo; Rosini, Michela; Minarini, Anna; Romanelli, Maria Novella; Dei, Silvia
- Abstract
Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer's disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting as acetylcholinesterase inhibitors (AChEIs), provide only symptomatic relief. Thus, the urgent need in AD drug development is for disease-modifying therapies that may require approaching targets from more than one path at once or multiple targets simultaneously. Indeed, increasing evidence suggests that the modulation of a single neurotransmitter system represents a reductive approach to face the complexity of AD. Memantine is viewed as a privileged NMDAR-directed structure, and therefore, represents the driving motif in the design of a variety of multi-target directed ligands (MTDLs). In this review, we present selected examples of small molecules recently designed as MTDLs to contrast AD, by combining in a single entity the amantadine core of memantine with the pharmacophoric features of known neuroprotectants, such as antioxidant agents, AChEIs and Aβ-aggregation inhibitors.
- Subjects
ALZHEIMER'S disease; DONEPEZIL; MEMANTINE; METHYL aspartate receptors; ACETYLCHOLINESTERASE inhibitors; SMALL molecules
- Publication
Molecules, 2020, Vol 25, Issue 17, p4005
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25174005