Huperzine A represents a novel alkaloid structure isolated from Huperzia serrata (Thunb.) Trev. = Lycopodium serratum Thunb., a Chinese folklore medicine. This compound appears to function as a highly efficacious cholinesterase inhibitor which has found use in China as a nootropic agent in the treatment of senile dementia of the Alzheimer's type and myasthenia gravis. Through the synthesis and in vitro biological testing of a variety of huperzine analogues it is our aim to discover: (a) the extent to which huperzine can be simplified to arrive at analogues that retain anticholinesterase activity; and (b) the structural parameters which are important for improving on the potency of action of huperzine. Through the achievement of these aims not only should we acquire knowledge essential to generating a more efficacious nootropic agent, but we should gain a better understanding of the structural and the stereochemical aspects of the cholinesterase site.
| Tang, X C; Kindel, G H; Kozikowski, A P et al. (1994) Comparison of the effects of natural and synthetic huperzine-A on rat brain cholinergic function in vitro and in vivo. J Ethnopharmacol 44:147-55 |
| Hanin, I; Tang, X C; Kindel, G L et al. (1993) Natural and synthetic Huperzine A: effect on cholinergic function in vitro and in vivo. Ann N Y Acad Sci 695:304-6 |
| Kozikowski, A P; Miller, C P; Yamada, F et al. (1991) Delineating the pharmacophoric elements of huperzine A: importance of the unsaturated three-carbon bridge to its AChE inhibitory activity. J Med Chem 34:3399-402 |
| McKinney, M; Miller, J H; Yamada, F et al. (1991) Potencies and stereoselectivities of enantiomers of huperzine A for inhibition of rat cortical acetylcholinesterase. Eur J Pharmacol 203:303-5 |
