Management of moderate to severe Alzheimer's disease: focus on memantine.
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.
Department of Bioscience Technology, Chung Yuan Christian University, Chung Li, Taiwan.
Evangelyn
E
Dominguez
Ting-Yu
TY
Chin
Chih-Ping
CP
Chen
Tzong-Yuan
TY
Wu
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D015259:Dopamine Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine