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Rationale for Combination Therapy With Galantamine and Memantine in Alzheimer's Disease
Author(s) -
Grossberg George T.,
Edwards Keith R.,
Zhao Qinying
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006288735
Subject(s) - galantamine , memantine , acetylcholinesterase , acetylcholinesterase inhibitor , alzheimer's disease , pharmacology , medicine , cholinergic , donepezil , rivastigmine , disease , glutamatergic , acetylcholine , glutamate receptor , neuroscience , psychology , dementia , receptor , chemistry , biochemistry , enzyme
A combination of cholinergic and glutamatergic dysfunction appears to underlie the symptomatology of Alzheimer's disease. Therefore, one hypothesis is that treatment strategies should address impairments in both systems. Galantamine is an acetylcholinesterase inhibitor that, unlike other acetylcholinesterase inhibitors, has a postulated dual mode of action as a nicotinic receptor modulator. Galantamine has demonstrated long‐term efficacy in improving or maintaining cognition, functionality, and behavior in patients with mild to moderate Alzheimer's disease. Memantine, a noncompetitive N ‐methyl‐ d ‐aspartate‐receptor antagonist, reduces deterioration in cognition and function in patients with moderate to severe Alzheimer's disease. Pharmacokinetic and pharmacodynamic as well as ongoing observation studies support the concept of adjunctive therapy with memantine in patients with advanced moderate Alzheimer's disease currently treated with an established galantamine regimen. The potential to modulate both acetylcholine and glutamate pathways in Alzheimer's disease presents a novel treatment strategy for the management of mild to moderately severe Alzheimer's disease.