Potencies and stereoselectivities of enantiomers of huperzine A for inhibition of rat cortical acetylcholinesterase.
The stereoselectivities and mechanisms of the inhibition of rat cortical acetylcholinesterase by the enantiomers of huperzine A were determined. (-)-Huperzine A was the more potent enantiomer with a Ki value of 8 nM. (+)-Huperzine A inhibited the enzyme 38-fold less potently with a Ki value of 300 nM. Racemic huperzine A was about two-fold less potent than the more active isomer, (-)-huperzine A. The mechanism of inhibition of acetylcholinesterase for all three drugs was of the mixed linear competitive type.
McKinney
M
M
Mayo Clinic Jacksonville, FL 32224.
Miller
J H
JH
Yamada
F
F
Tuckmantel
W
W
Kozikowski
A P
AP
D000470:Alkaloids; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D012717:Sesquiterpenes; C050426:huperzine A