Rationale for combination therapy with galantamine and memantine in Alzheimer's disease.
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.
Grossberg
George T
GT
Division of Geriatric Psychiatry, Department of Psychiatry, Saint Louis University, 1221 S. Grand Boulevard, St. Louis, MO 63104, USA. grossbgt@slu.edu
Edwards
Keith R
KR
Zhao
Qinying
Q
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077265:Donepezil; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005702:Galantamine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008559:Memantine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012720:Severity of Illness Index
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D005702:Galantamine; D000077265:Donepezil; D008559:Memantine