Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylcholine / metabolism*
-
Acetylcholinesterase / drug effects*
-
Acetylcholinesterase / metabolism
-
Alkaloids
-
Alzheimer Disease / drug therapy
-
Alzheimer Disease / enzymology
-
Alzheimer Disease / physiopathology
-
Animals
-
Brain Chemistry / drug effects
-
Brain Chemistry / physiology
-
Carbamates / pharmacology*
-
Carbamates / therapeutic use
-
Cerebral Cortex / drug effects*
-
Cerebral Cortex / enzymology
-
Cholinesterase Inhibitors / pharmacology
-
Cholinesterase Inhibitors / therapeutic use
-
Donepezil
-
Dose-Response Relationship, Drug
-
Fasciculation / chemically induced
-
Fasciculation / physiopathology
-
Indans / pharmacology*
-
Indans / therapeutic use
-
Male
-
Neurons / drug effects
-
Neurons / enzymology
-
Phenylcarbamates*
-
Piperidines / pharmacology*
-
Piperidines / therapeutic use
-
Rats
-
Rats, Sprague-Dawley
-
Rivastigmine
-
Sesquiterpenes / pharmacology*
-
Sesquiterpenes / therapeutic use
-
Up-Regulation / drug effects
-
Up-Regulation / physiology
Substances
-
Alkaloids
-
Carbamates
-
Cholinesterase Inhibitors
-
Indans
-
Phenylcarbamates
-
Piperidines
-
Sesquiterpenes
-
huperzine A
-
Donepezil
-
Acetylcholinesterase
-
Acetylcholine
-
Rivastigmine