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Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata. and in varying quantities in other Huperzia species, including H. elmeri, H. carinat, and H. aqualupian.
Huperzine A is also an acetylcholinesterase inhibitor, which has a mechanism of action similar to donepezil, rivastigmine, and galantamine. A pro-drug form of huperzine A (ZT-1) is under development as a treatment for Alzheimer's disease.
In the US, huperzine A is sold as a dietary supplement for memory support. The botanical has been used in China for centuries for the treatment of swelling, fever and blood disorders. Clinical trials in China have shown it to be effective in improving cognitive performance in patients with Alzheimer's disease and enhancing memory in students.
Pharmacological effects 
Huperzine A has also attracted the attention of US medical science. It is currently being investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer's disease. It has been found to be an inhibitor of the enzyme acetylcholinesterase. The structure of the complex of huperzine A with acetylcholinesterase has been determined by X-ray crystallography (PDB code: 1VOT; see the 3D structure). This is the same mechanism of action of pharmaceutical drugs such as galantamine and donepezil used to treat Alzheimer's disease. Huperzine A is also a NMDA receptor antagonist which may either reduce or increase glutamate induced damage in brain and increase nerve growth factor levels in rats.
Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be safer in terms of side effects. The National Institute on Aging has completed a Phase II clinical trial to evaluate the safety and efficacy of huperzine A in the treatment of Alzheimer's disease in a randomized controlled trial of its effect on cognitive function. In 2008, the National Institute on Aging conducted the first controlled trial outside of China evaluating the efficacy and toxicity of huperzine A to improve cognitive function in patients with AD. In this multi-center, double-blind, placebo-controlled Phase II trial, 210 participants with mild to moderate AD received either 200 mcg of huperzine A, 400 mcg of huperzine A, or placebo twice daily for 16 weeks. While no statistical difference in cognitive scores was noted in patients in the lower dose huperzine A group compared to placebo, the higher dose (400 mcg) of huperzine A led to improved cognition and activities of daily living. However, no significant changes were noted in any of the three groups in overall change in disease or in psychiatric ratings according to the AD Assessment Scale-Cognitive (ADAS-Cog) scale. Huperzine A was safe and well tolerated in the study. (13) The same year, a Cochrane Database review examined studies evaluating the efficacy and safety of huperzine A in the treatment of AD. The review included six randomized, controlled trials involving 454 patients. Huperzine A seemed to have beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and function performance with no serious side effects for patients with AD.
Possible side effects include breathing problems, tightness in the throat or chest, chest pain, skin hives, rash, itchy or swollen skin, upset stomach, diarrhea, vomiting, hyperactivity and insomnia. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug.
See also 
- Kozikowski, Alan P.; Tueckmantel, Werner (1999). "Chemistry, Pharmacology, and Clinical Efficacy of the Chinese Nootropic Agent Huperzine A". Accounts of Chemical Research 32 (8): 641–650. doi:10.1021/ar9800892.
- Lim WH, Goodger JQ, Field AR, Holtum JA, Woodrow IE "Huperzine alkaloids from Australasian and southeast Asian Huperzia". Pharm Biol. 2010 Sep;48(9):1073-8
- P. Scalfaro, V. Nicolas, M.P. Simonin, S. Charbon, M. McCormick, F. Heimgartner. The sustained release of the acetylcholinesterase inhibitor ZT-1 confers the potential for a more efficient neuroprotection in rats. Neurobiology of Aging Conference in New Orleans, Nov 2003.
- Wang, Bai-Song; Wang, Hao; Wei, Zhao-hui; Song, Yan-yan; Zhang, Lu; Chen, Hong-Zhuan (2009). "Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis". Journal of Neural Transmission 116 (4): 457. doi:10.1007/s00702-009-0189-x. PMID 19221692.
- Sun, QQ; Xu, SS; Pan, JL; Guo, HM; Cao, WQ (1999). "Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students.". Zhongguo yao li xue bao = Acta pharmacologica Sinica 20 (7): 601–3. PMID 10678121.
- Wang, BS; Wang, H; Wei, ZH; Song, YY; Zhang, L; Chen, HZ (2009). "Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.". Journal of neural transmission (Vienna, Austria : 1996) 116 (4): 457–65. doi:10.1007/s00702-009-0189-x. PMID 19221692.
- Coleman, BR; Ratcliffe, RH; Oguntayo, SA; Shi, X; Doctor, BP; Gordon, RK; Nambiar, MP (2008). "+-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats.". Chemico-biological interactions 175 (1-3): 387–95. doi:10.1016/j.cbi.2008.05.023. PMID 18588864.
- Zangara, A (2003). "The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease". Pharmacol Biochem Behav. 75 (3): 675–86. doi:10.1016/S0091-3057(03)00111-4. PMID 12895686.
- Bai, D. L.; Tang, X. C.; He, X. C. (2000). "Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease". Current Medicinal Chemistry 7 (3): 355–374. PMID 10637369.
- Tang, X. C.; He, X. C.; Bai, D. L. (1999). "Huperzine A: a novel acetylcholinesterase inhibitor". Drugs of the Future 24 (6): 647–663. doi:10.1358/dof.1999.024.06.545143.
- Raves, ML; Harel, M; Pang, Y-P; Silman, I; Kozikowski, AP; Sussman, JL (1997). "3D structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A.". Nature Struct Biol 4 (1): 57–63. PMID 8989325.
- Tang, L., Wang, R., Tang, X. (2005). "Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells". Acta Pharmacologica Sinica 26 (6): 673–678. doi:10.1111/j.1745-7254.2005.00130.x. PMID 15916732.
- Huperzine A, Alzheimer Research Forum
- Tun, M.K.M.; Wüstmann, D-J.; Herzon, S.B. (2011). "A robust and scalable synthesis of the potent neuroprotective agent (−)-huperzine A .". Chemical Science 2: 2251–2253. doi:10.1039/C1SC00455G.
- Tudhope, S. R.; Bellamy, J. A.; Ball, A.; Rajasekar, D.; Azadi-Ardakani, M.; Meera, H. S.; Gnanadeepam, J. M.; Saiganesh, R. et al. (2012). "Development of a Large-Scale Synthetic Route to Manufacture (−)-Huperzine A". Organic Process Research & Development 16 (4): 635. doi:10.1021/op200360b.