title: Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex.
abstract: Based on surrogate assays of peripheral red blood cells, reports state that widely prescribed doses of donepezil hydrochloride provide nearly complete inhibition of cerebral cortical acetylcholinesterase activity in the treatment of Alzheimer's disease (AD). To test this, direct positron emission tomography measures of cerebral acetylcholinesterase activity were made in AD patients before and after treatment with donepezil (5 and 10 mg/day) for at least 5 weeks and compared with similar measures in normal controls who were untreated or after acute administration of another AChE inhibitor, physostigmine salicylate (1.5 mg/hr). After physostigmine, acetylcholinesterase inhibition averaged 52% in normal cerebral cortex. After donepezil, cerebral cortical inhibition in AD brain averaged only 27%. Clinical trials of this donepezil dose schedule are not testing the effect of nearly complete cerebral cortical inhibition.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Kuhl
authors.forename: S
authors.initials: S
authors.lastname: Minoshima
authors.forename: K A
authors.initials: KA
authors.lastname: Frey
authors.forename: N L
authors.initials: NL
authors.lastname: Foster
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D002800:Cholinesterase Inhibitors / Q000378:metabolism* / Q000627:therapeutic use*; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000378:metabolism* / Q000627:therapeutic use*; D008875:Middle Aged; D010830:Physostigmine / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism* / Q000627:therapeutic use*; D014055:Tomography, Emission-Computed
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D010830:Physostigmine; D000110:Acetylcholinesterase