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.