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Huperzine A is an acetylcholinesterase inhibititor<ref name="Alzheimer 1996">{{cite journal|pmid=19221692|year=2009|last1=Wang|first1=BS|last2=Wang|first2=H|last3=Wei|first3=ZH|last4=Song|first4=YY|last5=Zhang|first5=L|last6=Chen|first6=HZ|title=Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.|volume=116|issue=4|pages=457–65|doi=10.1007/s00702-009-0189-x|journal=Journal of neural transmission (Vienna, Austria : 1996)}}</ref> and [[NMDA receptor]] antagonist,<ref>{{cite journal|pmid=18588864|year=2008|last1=Coleman|first1=BR|last2=Ratcliffe|first2=RH|last3=Oguntayo|first3=SA|last4=Shi|first4=X|last5=Doctor|first5=BP|last6=Gordon|first6=RK|last7=Nambiar|first7=MP|title=+-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats.|volume=175|issue=1-3|pages=387–95|doi=10.1016/j.cbi.2008.05.023|journal=Chemico-biological interactions}}</ref>.
Huperzine A is an acetylcholinesterase inhibititor<ref name="Alzheimer 1996">{{cite journal|pmid=19221692|year=2009|last1=Wang|first1=BS|last2=Wang|first2=H|last3=Wei|first3=ZH|last4=Song|first4=YY|last5=Zhang|first5=L|last6=Chen|first6=HZ|title=Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.|volume=116|issue=4|pages=457–65|doi=10.1007/s00702-009-0189-x|journal=Journal of neural transmission (Vienna, Austria : 1996)}}</ref> and [[NMDA receptor]] antagonist,<ref>{{cite journal|pmid=18588864|year=2008|last1=Coleman|first1=BR|last2=Ratcliffe|first2=RH|last3=Oguntayo|first3=SA|last4=Shi|first4=X|last5=Doctor|first5=BP|last6=Gordon|first6=RK|last7=Nambiar|first7=MP|title=+-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats.|volume=175|issue=1-3|pages=387–95|doi=10.1016/j.cbi.2008.05.023|journal=Chemico-biological interactions}}</ref>.


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]].<ref>{{cite journal|author = Zangara, A|title = The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease|journal = Pharmacol Biochem Behav.|year = 2003|volume = 75|issue = 3|pages = 675–86|doi = 10.1016/S0091-3057(03)00111-4|pmid = 12895686}}</ref><ref name=r1>{{cite journal|author = Bai, D. L.; Tang, X. C.; He, X. C.|title = Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease|pmid=10637369|journal = Current Medicinal Chemistry|year = 2000|volume = 7 |issue= 3|pages = 355–374}}</ref> It has been found to be an [[enzyme inhibitor|inhibitor]] of the enzyme [[acetylcholinesterase]].<ref>{{cite journal|author = Tang, X. C.; He, X. C.; Bai, D. L.|title = Huperzine A: a novel acetylcholinesterase inhibitor|journal = Drugs of the Future|year = 1999|volume = 24|issue = 6|pages = 647–663|doi = 10.1358/dof.1999.024.06.545143}}</ref> The structure of the complex of huperzine A with acetylcholinesterase has been determined by [[X-ray crystallography]] (PDB code: [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vot 1VOT]; [http://www.proteopedia.org/wiki/index.php/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]] [[receptor antagonist|antagonist]] which protects the brain against glutamate induced damage, and it appears to increase [[nerve growth factor]] levels in rats.<ref>{{cite journal|author = Tang, L., Wang, R., Tang, X.|title = Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells|journal = Acta Pharmacologica Sinica|year = 2005|volume = 26|pages = 673–678|doi = 10.1111/j.1745-7254.2005.00130.x|pmid = 15916732|issue = 6}}</ref>
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]].<ref>{{cite journal|author = Zangara, A|title = The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease|journal = Pharmacol Biochem Behav.|year = 2003|volume = 75|issue = 3|pages = 675–86|doi = 10.1016/S0091-3057(03)00111-4|pmid = 12895686}}</ref><ref name=r1>{{cite journal|author = Bai, D. L.; Tang, X. C.; He, X. C.|title = Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease|pmid=10637369|journal = Current Medicinal Chemistry|year = 2000|volume = 7 |issue= 3|pages = 355–374}}</ref> It has been found to be an [[enzyme inhibitor|inhibitor]] of the enzyme [[acetylcholinesterase]].<ref>{{cite journal|author = Tang, X. C.; He, X. C.; Bai, D. L.|title = Huperzine A: a novel acetylcholinesterase inhibitor|journal = Drugs of the Future|year = 1999|volume = 24|issue = 6|pages = 647–663|doi = 10.1358/dof.1999.024.06.545143}}</ref> The structure of the complex of huperzine A with acetylcholinesterase has been determined<ref>{{cite journal|pmid= 8989325|year=1997|last1= Raves |first1=ML|last2=Harel|first2=M|last3=Pang|first3=Y-P|last4=Silman|first4=I|last5=Kozikowski|first5=AP|last6=Sussman|first6=JL|title=3D structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A.|volume=4|issue=1|pages=57-63|journal=Nature Struct Biol}}</ref>. by [[X-ray crystallography]] (PDB code: [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vot 1VOT]; [http://www.proteopedia.org/wiki/index.php/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]] [[receptor antagonist|antagonist]] which protects the brain against glutamate induced damage, and it appears to increase [[nerve growth factor]] levels in rats.<ref>{{cite journal|author = Tang, L., Wang, R., Tang, X.|title = Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells|journal = Acta Pharmacologica Sinica|year = 2005|volume = 26|pages = 673–678|doi = 10.1111/j.1745-7254.2005.00130.x|pmid = 15916732|issue = 6}}</ref>


Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be a bit safer in terms of side effects.<ref name=china/> The [[National Institute on Aging]] has completed<ref name=r1/> a Phase II clinical trial<ref>[http://www.alzforum.org/drg/drc/detail.asp?id=53 Huperzine A], Alzherimer Research Forum</ref> 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.
Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be a bit safer in terms of side effects.<ref name=china/> The [[National Institute on Aging]] has completed<ref name=r1/> a Phase II clinical trial<ref>[http://www.alzforum.org/drg/drc/detail.asp?id=53 Huperzine A], Alzherimer Research Forum</ref> 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.

Revision as of 22:07, 10 November 2011

Huperzine A
Huperzine A
Huperzine A 3d
Names
IUPAC name
(1R,9S,13E)- 1-Amino- 13-ethylidene- 11-methyl- 6-azatricyclo[7.3.1.02,7] trideca- 2(7),3,10- trien- 5-one
Other names
HupA
Identifiers
3D model (JSmol)
ChemSpider
DrugBank
ECHA InfoCard 100.132.430 Edit this at Wikidata
  • InChI=1S/C15H18N2O/c1-3-11-10-6-9(2)8-15(11,16)12-4-5-14(18)17-13(12)7-10/h3-6,10H,7-8,16H2,1-2H3,(H,17,18)/b11-3+/t10-,15+/m0/s1 checkY
    Key: ZRJBHWIHUMBLCN-YQEJDHNASA-N checkY
  • InChI=1/C15H18N2O/c1-3-11-10-6-9(2)8-15(11,16)12-4-5-14(18)17-13(12)7-10/h3-6,10H,7-8,16H2,1-2H3,(H,17,18)/b11-3+/t10-,15+/m0/s1
    Key: ZRJBHWIHUMBLCN-YQEJDHNABN
  • C\C2=C\[C@H]\3CC=1NC(=O)\C=C/C=1[C@@](N)(C2)C/3=C\C
Properties
C15H18N2O
Molar mass 242.32 g/mol
Melting point 217–219 °C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the plant firmoss Huperzia serrata.[1]

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.[2]

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 the treatment of Alzheimer's disease[3] and enhancing memory in students.[4]

Pharmacological effects

Huperzine A is an acetylcholinesterase inhibititor[5] and NMDA receptor antagonist,[6].

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.[7][8] It has been found to be an inhibitor of the enzyme acetylcholinesterase.[9] The structure of the complex of huperzine A with acetylcholinesterase has been determined[10]. 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 protects the brain against glutamate induced damage, and it appears to increase nerve growth factor levels in rats.[11]

Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be a bit safer in terms of side effects.[3] The National Institute on Aging has completed[8] a Phase II clinical trial[12] 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.

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.[5]

See also

References

  1. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ 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.
  3. ^ a b 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.
  4. ^ 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.
  5. ^ a b 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ a b 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ 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.
  11. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Huperzine A, Alzherimer Research Forum
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