Management of moderate to severe Alzheimer's disease: focus on memantine
Evangelyn Dominguez1, Ting-Yu Chin, Chih-Ping Chen
1Department of Bioscience Technology, Chung Yuan Christian University, Chung Li, Taiwan.
Abstract:
Alzheimer's disease (AD) is the most common form of dementia, and one of the principal causes leading to death around the world. It is a progressive neurodegenerative disorder that still remains without definite cure. Memantine, a licensed AD drug, is an open-channel and partial trapping blocker that functions as a potent NMDA receptor antagonist, even at low concentrations. Aside from being uncompetitive, it also allows near-normal physiological NMDA receptor activity throughout the brain even with high glutamate concentrations, making it more reliable and tolerable than other AD-targeted drugs. It has also been found to be effective, safe, and well-tolerated in animal models as well as patients with moderate-to-severe AD. Aside from NMDA receptor antagonism, numerous studies have reported that memantine can also affect dopamine receptors, block excessive calcium influx and production of reactive oxygen species (ROS) induced by Aβ oligomers, and inhibit the internal ribosome entry site (IRES), thus preventing the expression of the amyloid precursor and tau proteins which are considered as early indicators of Alzheimer's.
Insights
Memantine, an Alzheimer's disease (AD) drug, acts as an NMDA receptor antagonist. It offers a safer and more tolerable treatment option by modulating neurotransmission and preventing the expression of key AD proteins.
Area of Science:
- Neuroscience
- Pharmacology
- Dementia Research
Background:
- Alzheimer's disease (AD) is a leading cause of death globally, characterized by progressive neurodegeneration with no definitive cure.
- Memantine is an approved medication for AD, functioning as an NMDA receptor antagonist.
Purpose of the Study:
- To elucidate the multifaceted mechanisms of memantine beyond NMDA receptor antagonism in Alzheimer's disease.
- To highlight memantine's therapeutic potential in managing moderate-to-severe AD.
Main Methods:
- Review of existing literature on memantine's pharmacological actions.
- Analysis of studies investigating memantine's effects on various cellular and molecular pathways implicated in AD.
Main Results:
- Memantine exhibits NMDA receptor antagonism, allowing physiological activity even with high glutamate levels, enhancing tolerability.
- Additional effects include modulation of dopamine receptors, blocking calcium influx, reducing reactive oxygen species (ROS), and inhibiting IRES-mediated translation.
- These actions collectively prevent the expression of amyloid precursor and tau proteins, crucial early indicators of AD.
Conclusions:
- Memantine's therapeutic benefits extend beyond NMDA receptor antagonism, involving multiple pathways relevant to AD pathology.
- Its unique mechanism offers a safer and well-tolerated treatment for moderate-to-severe Alzheimer's disease.
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