Huperzine A, a novel promising acetylcholinesterase inhibitor.
The effects of huperzine A on memory impairments induced by scopolamine were evaluated using a radial maze task and inhibition of cholinesterase in vitro compared with the effects of E2020 and tacrine. Scopolamine (0.2 mg kg-1) significantly impaired spatial memory in rats. Huperzine A (0.1-0.4 mg kg-1, p.o.), E2020 (0.5-1.0 mg kg-1, p.o.) and tacrine (1.0-2.0 mg kg-1, p.o.) could reverse these scopolamine-induced memory deficits. The ratios of huperzine A, E2020 and tacrine for butyrylcholinesterase:acetylcholinesterase determined by a colourimetric method were 884.57, 489.05, and 0.80, respectively. The results demonstrated that huperzine A was the most selective acetylcholinterase inhibitor, and improved the working memory deficit induced by scopolamine significantly better than did E2020 or tacrine, suggesting it may be a promising agent for clinical therapy of cognitive impairment in patients with Alzheimer's Disease.
Cheng
D H
DH
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, P.R. China.
Ren
H
H
Tang
X C
XC
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D013619:Tacrine / Q000494:pharmacology / Q000627:therapeutic use
D000470:Alkaloids; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D012717:Sesquiterpenes; C050426:huperzine A; D013619:Tacrine; D000077265:Donepezil; D012601:Scopolamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase