Huperzine A is a plant alkaloid derived from the Chinese club moss plant, Huperzia serrata, which is a member of the Lycopodium species. Huperzia serrata has been used in Chinese folk medicine for the treatment of fevers and inflammation.
Huperzine A has been found to have acetylcholinesterase activity. Huperzine B, also derived from Huperzia serrata, is a much less potent acetylcholinesterase inhibitor. Natural huperzine A is a chiral molecule also called L-huperzine A or (-)-huperzine A. Synthetic huperzine A is a racemic mixture called (±)-huperzine A. Huperzine A is also known as HUP, hup A and selagine. In Chinese medicine, the extract of Huperzia serrata is known as Chien Tseng Ta and shuangyiping. Huperzine A derivatives are being developed for pharmaceutical application.
Huperzine A is believed to have a synergistic effect when combined with cholinesterase inhibitors, drugs that act in a similar fashion to combat Alzheimer's-related memory loss. So while the combination of these two agents could potentially boost the benefits of both, it could also lead to as yet unidentified negative reactions. Mental improvements associated with huperzine A appear to stem from the compound's ability to inhibit the breakdown of acetylcholine, a brain chemical essential to memory. The only Alzheimer's drugs currently approved by the U.S. Food and Drug Administration work in much the same way. In fact, laboratory findings indicate that huperzine A may be more precise than conventional medications in the manner in which it protects acetylcholine, raising hopes that it could counter memory loss with relatively few side effects.
Alzheimer's disease is a neurodegenerative disorder associated with neuritic plaques that affect the cerebral cortex, amygdala and hippocampus. There is also neurotransmission damage in the brain. One of the major functional deficits in Alzheimer's disease is a hypofunction of cholinergic neurons. This leads to the cholinergic hypothesis of Alzheimer's disease and the rationale for strategies to increase acetylcholine in the brains of Alzheimer's disease patients. Two FDA-approved drugs for the treatment of Alzheimer's disease, tacrine and donepezil, are acetylcholinesterase inhibitors.
Huperzine A is also an acetylcholinesterase inhibitor and has been found to increase acetylcholine levels in the rat brain following its administration. It also increases norepinephrine and dopamine, but not serotonin levels. The natural L or (-)-huperzine A is approximately three times more potent than the racemic or (±)-huperzine A in vitro.