Similar potency of the enantiomers of huperzine A in inhibition of [H-3]dizocilpine (MK-801) binding in rat cerebral cortex

The inhibition of huperzine A, a potential therapeutic agent to treat Alzhe imer's disease, on rat cortical acetylcholinesterase was found to be highly stereospecific. In the present study the effect of the enantiomers of hupe rzine A on [H-3]dizocilpine (MK-801) binding to synaptic membrane of rat ce rebral cortex was compared. The natural (-)-huperzine A and the synthetic ( +)-huperzine A inhibited the specific binding of [H-3]MK-801 with a similar potency. The IC50 values were:65 +/- 7 and 82 +/- 12 muM (n = 5 for each e nantiomer, P = 0.248), respectively. The result indicates that huperzine A inhibits N-methyl-D-aspartate (NM DA) receptor in rat cerebral cortex witho ut stereoselectivity. (C) 2000 Elsevier Science Ireland Ltd. All rights res erved.