Memory improvement without toxicity during chronic, low dose intravenous arecoline in Alzheimer's disease.
Arecoline, a cholinergic agonist, administered at low doses by continuous intravenous infusion for up to 2 weeks, significantly and replicably improved memory in five of nine subjects with mild-moderate Alzheimer's disease. During dose finding, performance on a verbal memory task improved with an inverted U-shaped relation to dose. Six of nine subjects were classified as responders. During blinded, placebo-controlled, individualized optimal dosing for 5 days, verbal memory again improved in five of six responders but not in any non-responder. No adverse drug effects occurred. Arecoline, and possibly other cholinergic agonists, can safely improve memory in Alzheimer's disease at doses much lower than previously studied.
Soncrant
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TT
Unit on Pharmacology and Pharmacokinetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
Raffaele
K C
KC
Asthana
S
S
Berardi
A
A
Morris
P P
PP
Haxby
J V
JV
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D001115:Arecoline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects
D001115:Arecoline