Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats.
The cholinesterase inhibitors huperzine A, donepezil and rivastigmine were compared for their effects on extracellular acetylcholine concentration and acetylcholinesterase activity in the rat cortex. After i.p. injection, huperzine A (0.25-0.75 micromol/kg), donepezil (2-6 micromol/kg) and rivastigmine (0.75-1.5 micromol/kg) dose-dependently elevated the concentration of acetylcholine. The duration of huperzine A was longest. The time courses of cortical acetylcholinesterase inhibition with middle doses of these agents mirrored the increases of acetylcholine at the same doses. However, acetylcholinesterase inhibition was disproportionately greater after middle dose of rivastigmine than doses of huperzine A and donepezil that increased acetylcholine to a similar extent. Muscle fasciculation appeared only after donepezil with a dose-dependent incidence and intensity. In molar terms, huperzine A was 8- and 2-fold more potent than donepezil and rivastigmine, respectively, in increasing cortical acetylcholine levels, with a longer-lasting effect.
Liang
Yan Qi
YQ
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
Tang
Xi Can
XC
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002219:Carbamates / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005207:Fasciculation / Q000139:chemically induced / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D048448:Phenylcarbamates; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068836:Rivastigmine; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000470:Alkaloids; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D012717:Sesquiterpenes; C050426:huperzine A; D000077265:Donepezil; D000110:Acetylcholinesterase; D000109:Acetylcholine; D000068836:Rivastigmine