Huperzine A

Description:

An extract from a variety of the Chinese club moss, Huperzia serrata. Studies carried out in China indicated that the active substance Huperzine A, is a promising new treatment for Alzheimer’s disease. Other studies indicate that Huperzine A is a superior acetylcholine esterase (AChE) inhibitor with excellent penetration into the CNS and a remarkable in vivo half-life. Two double-blind clinical trials carried out in China demonstrate that Huperzine A is both safe and effective for the long term treatment of Alzheimer's dementia. In addition to its activity as an AChE inhibitor, recent findings suggest that Huperzine A has other neuroprotective functions:

1) Huperzine A inhibits glutamate-induced cytotoxicity in cultures of rat neonatal hippocampal and cerebella neurons;

2) Huperzine A promotes dendrite outgrowth of neuronal cultures.

Alzheimer’s disease is characterized by abnormalities and degeneration of neurons which depend upon acetylcholine and acetylcholine esterase for normal activity and viability. These cells located in the basal forebrain are also implicated in other neurological diseases such as Parkinson’s disease. Huperzine A is a potent inhibitor of acetylcholine esterase, superior in activity to TACRINE, the first drug licensed in the USA for Alzheimer’s disease and E2020 which was licensed recently by Eisai Pharmaceuticals. In addition, Huperzine A has been shown to protect neuronal cells in culture from death caused by the excitoamino acid glutamate. Because of the dual pharmacological action of Huperzine A, HuperazonTM provides a unique and important activity for the treatment of AD and senile memory deficits.

Toxicology and efficacy studies of Huperzine A show it to be non-toxic even when administered at 50-100 times the human therapeutic dose. The extract is active for 6 hours at a dose of 2 µg/kg with no remarkable side effects.

In Alzheimer’s disease, double blind controlled studies of over 160 patients, showed significant improvement measured by Weschler scale results, at doses of only 150 µg given twice daily (3-5 µg/kg). Figure 1 below presents representative clinical data on Huperzine A. The upper panel presents an assessment of the patients by their caretakers comparing Huperzine A with a placebo. The lower panel shows the improvement in memory comparing Huperzine A to piracetam.

Figure 1: Representative clinical studies of Huperzine A.

Two important characteristics of Huperzine A distinguish it from TACRINE and E2020 as well as other experimental compounds in development. Huperzine A is highly specific for brain acetylcholine esterase (AChE) vs. AChE found elsewhere in the body. This selectivity is believed to be responsible for the relatively low toxicity of the extract. In addition, unlike the two approved drugs for Alzheimer’s disease, TACRINE and E2020, Huperzine A has been shown to lack binding to receptors in the CNS that can cause side effects such as the muscarinic receptors M1 and M2.

The duration of action of Huperzine A at 3 hours is superior to TACRINE (2 hours) and physostigmine (30 minutes). In behavioral experiments of learning and memory enhancement in animals, the difference between amounts of the extract effective for memory and learning and the no-toxic-effect dose (from toxicity studies) was 30-100 fold. These data strongly suggest that Huperzine A can be useful in treating Alzheimer’s disease with minimal side effects.

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