Huperzine A: A New Memory Enhancing Drug Based on Chinese Herbal Medicine

Huperzine A, a compound isolated from the Chinese Medicinal Herb “Qian Ceng Ta,” has shown good efficacy in improving the memory in patients suffering from Alzheimer’s Disease. Despite these promising results, Huperzine A has not been developed as a drug in the West due to scarcity of the natural source, a complicated molecular structure, and the lack of intellectual property protection for this material.

Virginia Tech researcher Paul R. Carlier, an associate professor of chemistry, has come up with a novel solution to these problems. Carlier will present his research at the 220th national meeting of the American Chemical Society Aug. 20-24 in Washington, D.C.

Working in collaboration with researchers at the Hong Kong University of Science and Technology (HKUST) and the Mayo Clinic, Carlier found that a highly simplified fragment of the Huperzine A molecule could be easily synthesized from cheap, commercially available chemicals. In isolation this fragment is ineffective as a memory enhancer. However, based on a detailed analysis of acetylcholinesterase, the brain enzyme with which Huperzine A interacts, Carlier prepared dimeric analogs by joining two of these fragments with a molecular tether.

“Remarkably, the optimum drug obtained by this approach, (‘Huperzine A Fragment Dimer’) is more than twice as potent as Huperzine A itself,” he reports. “The enhanced potency observed is due to two-point attachment of the dimeric drug to acetylcholinesterase,” he says.

Carlier stresses that all of the tests have been in animals, including a behavioral assay in rats that establishes improved memory. “No work has been done in humans; and, even if the compounds prove effective in human, it will be as a treatment of the memory loss in the early stages of the disease,” he says. “This approach could never cure Alzheimer’s; and, after the disease progresses to a certain point, these drugs could not restore mental function.”

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