Pharmacology huperzines

Chemistry, pharmacology, and clinical efficacy of the Chinese nootropic agent huperzine A, alkaloid from Hupenia sermta with annulated 2-pyridone and l-amino-3-methyl-9-ethylidenebicyclo[3.3.l]nona-2,6-diene fragments 99ACR641. 

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. Pharmacology and Biochemistry Behaviour, 75 675-686. 

Jiang, H. L. Bai, D. L. Luo, X. M. Progress in clinic, pharmacological, chemical and structural biological studies of huperzine A a drug of traditional Chinese medicine origin for the treatment of Alzheimer s disease. Curr. Med. Chem., 2003, 10 2231-2252. 

Camps, R El Achab, R. Gorbig, D. M. Morral, J. Munoz-Torrero, D. Badia, A. Banos, J. E. Vivas, N. M. Barril, X. Orozco, M. Luque, F. J. Synthesis in vitro pharmacology and molecular modeling of very potent tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer s disease. J. Med. Chem., 1999, 42(17) 3227-3242. 

Huperzine A is not the only AChE inhibitor available from nature s storehouse. As one example, the unusual polyphenol hopeahainol A (94) was recently reported from Hopea hainanensis It has a comparable IC50 to huperzine A against AChE and was shown to be a reversible inhibitor of the enzyme. It is thus another example of the versatility of the plant kingdom in providing novel structures with pharmacological relevance. 

Biosynthesis The biosynthesis of the L. a. has not been completely elucidated. Since Lycopodium species cannot or can only be cultivated with difficulty, tracer experiments must be performed at the natural locations. It is certain that the biogenetic building blocks for the complex ring systems are lysine and acetate. Pharmacological activity The L. a. are moderately toxic. Some L. a. are purported to be potent inhibitors of acetylcholine esterase. Huperzine A has attracted attention on account of its stimulating effect on learning and memory behavior in laboratory animals. In Chinese traditional medicine various Lycopodium species are used to treat skin diseases and as a tonic. 

Acetylcholinesterase Alzheimer s disease biological activity clinical trials club mosses huperzine A Lycopodiaceae lycopodium alkaloids pharmacology... 

Ha GT, Wong RK, Zhang Y (2011) Huperzine A as potential treatment of Alzheimer s disease an assessment on chemistry, pharmacology, and clinical studies. Chem Biodivers 8(7) 1189-1204. doi 10.1002/cbdv.201000269... 

Pharmacology of Huperzine A (1) Total Synthesis of Huperzine A (1) SAR Studies of Huperzine A (1) Conclusions... 

This review describes the recent studies on Lycopodium alkaloids isolated from the genus Lycopodium and Huperzia, the proposed biogenetic pathway, and the syntheses of Lycopodium alkaloids based on these biogenetic proposals. In section II, all of the Lycopodium alkaloids isolated so far, and including our recent work, are surveyed, while sections III and IV mainly deal with the biogenetic pathways and the total syntheses of the Lycopodium alkaloids, respectively. In sections V, VI, and VII, pharmacology, total synthesis, and SAR studies, respectively of huperzine A (I) are briefly surveyed. 

Huperzine A (1) has undergone clinical trials in China in patients suffering from various memory disorders, including Alzheimer s disease. Significant effects of huperzine A (1) were noted in these patients in terms of their quality of life and it has become available to numerous individuals for the treatment of memory problems. Since the other pharmacological activities of the various types of Lycopodium alkaloids have been poorly studied, this area should also be developed. Similarly, the biosynthesis of Lycopodium alkaloids has been only preliminarily studied, and the pathways have not been characterized with respect to the intermediates and the relevant enzymes. It will further be of value to elucidate the structural and pharmacological features of more Lycopodium alkaloids. 

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