CHINESE HERB Treatment ALZHEIMERS #6

PHARMACOLOGY AND CLINICAL APPLICATIONS OF HUPERZINE

Huperzines A and B reversibly inhibit cholinesterase; huperzine A has a stronger action than huperzine B, which in turn has a stronger action than galanthamine (an alkaloid from Lycorus radiata that has been used for its anticholinesterase activity). Huperzine A has substantially stronger anticholinesterase activity than physostigmine or neostigmine (chinchona alkaloids obtained from Physostigma venenosum; neostigmine is a common drug for treatment of myasthenia at a dose of 1-2 mg by IM or 0.5 mg IV; physostigmine is also an approved anticholinesterase drug), but huperzine B is three to five times weaker than physostigmine. Huperzines A and B have greater effect on acetylcholinesterase (AChE) than on butyrocholinesterase (BuChE). Huperzine A, because of its cholinesterase inhibiting activity, has been used in myasthenia gravis patients in China, with apparent success.

Both huperzine A and B have been shown to have memory-enhancing activities in animals. At 0.075 mg/kg for huperzine A or 0.5 mg/kg for huperzine B, IP administration to mice significantly facilitated spatial discrimination learning in a Y-maze study. At slightly higher doses (0.075-0.125 mg/kg for A and 0.6-0.8 mg/kg for B) the huperzines given prior to exposure of mice to carbon dioxide prevented hypercapnia-induced impairment of learning. Memory retention and retrieval could be enhanced in animals when the alkaloids were given immediately or 6-12 hours after training. Substantially lower or higher doses of huperzines are not effective. Huperzine has been used for Alzheimer's and senile dementia with positive results. In a double-blind trial with a group of 56 patients suffering from multi-infarct dementia or senile dementia and a group of 104 patients with senile and presenile memory loss, huperzine A was demonstrated to be effective for improving memory. It was given by intramuscular injection, 0.05 mg twice daily for four weeks to the first group and 0.03 mg twice daily for two weeks to the second group. The only side effect was slight dizziness experienced by a few patients. In rats, fordine, at 0.01-0.04 mg/kg IP, speeds up conditioned avoidance responses, reverses impairment of conditioned avoidance response, and antagonizes hippocampal and cortical EEG changes induced by quinuclidinyl benilate.

Huperzine A has been evaluated at the Mayo Clinic in Jacksonville, Florida. According to Alan Kozikowski, a chemist who is heading the research there, Huperzine A is more effective and more specific than tacrine, another anticholinesterase drug. Interneuron Pharmaceuticals in Lexington, Mass. is testing Huperzine A in human clinical trials.

http://www.itmonline.org/arts/alzheimers.htm

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