title: No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use.
abstract: The loss of cholinergic neurons within the basal forebrain of patients with Alzheimer's disease (AD) may underlie aspects of the dementia. Excessive activation of N-methyl-D-aspartate (NMDA) receptors may underlie the degeneration of cholinergic cells. New drug therapies have been designed to either enhance cholinergic function by inhibition acetylcholinesterase (AChE), e.g. galanthamine, tetrahydroaminoacridine or donepezil, or by attenuation of NMDA receptor function, e.g. memantine. A combination of these two therapeutic approaches may be more beneficial at slowing the progression of the AD. The current study investigated whether memantine would attenuate the inhibition of AChE produced by these three drugs. The results indicate that these AChE inhibitors do not lose their therapeutic efficacy in combination with memantine. Our in vitro data suggest that the clinical combination of memantine with a reversible AChE inhibitor should be a valuable pharmacotherapeutic approach to dementia.
authors.affiliation: Division of Neural Systems, Memory & Aging, University of Arizona, Tucson 85724, USA. gary@nsma.arizona.edu
authors.forename: G L
authors.initials: GL
authors.lastname: Wenk
authors.forename: G
authors.initials: G
authors.lastname: Quack
authors.forename: H J
authors.initials: HJ
authors.lastname: Moebius
authors.forename: W
authors.initials: W
authors.lastname: Danysz
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005702:Galantamine / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013619:Tacrine / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D010880:Piperidines; D005702:Galantamine; D013619:Tacrine; D000077265:Donepezil; D000110:Acetylcholinesterase; D008559:Memantine