Huperzine A

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Huperzine A
Huperzine A
Huperzine A 3d
Identifiers
CAS number 102518-79-6 N
ChemSpider 16736021 YesY
UNII 0111871I23 N
DrugBank DB01928
ChEBI CHEBI:78330 N
ChEMBL CHEMBL395280 YesY
Jmol-3D images Image 1
Properties
Molecular formula C15H18N2O
Molar mass 242.32 g/mol
Melting point 217 to 219 °C (423 to 426 °F; 490 to 492 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata[1] and in varying quantities in other Huperzia species, including H. elmeri, H. carinat, and H. aqualupian.[2]

Huperzine A has been found, through multiple studies, to be effective as a medicine for helping people with neurological conditions such as Alzheimer's disease, but the meta-analysis of those studies concluded that they were poor quality and the findings should be interpreted with caution.[3][4]

Pharmacological effects[edit]

Huperzine A is extracted from Huperzia serrata.[1] It is a reversible acetylcholinesterase inhibitor[5][6] and NMDA receptor antagonist[7] that crosses the blood-brain barrier.[8] The structure of the complex of huperzine A with acetylcholinesterase has been determined by X-ray crystallography (PDB code: 1VOT; see the 3D structure).[9]

For some years, huperzine A has been investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer's disease.[1][10] A 2013 meta-analysis found that huperzine A may be efficacious in improving cognitive function, global clinical status, and activities of daily living for individuals with Alzheimer’s disease. However, due to the poor size and quality of the clinical trials reviewed, huperzine A should not be recommended as a treatment for Alzheimer’s disease until further high quality studies confirm its beneficial effects.[3]

Huperzine A is also marketed as a dietary supplement with claims made for its ability to improve memory and mental function.[11] Huperzine A may also have a possible role in the treatment of myasthenia gravis.[12]

Adverse effects[edit]

Huperzine A may present with mild cholinergic side effects such as nausea, vomiting and diarrhea.[4]

The use of huperzine A during pregnancy and lactation is not recommended due to the lack of sufficient safety data.[13]

Drug interactions[edit]

Huperzine A may decrease heart rate so it may have additive effects if taken with drugs causing bradycardia, such as beta-blockers.[12]

Theoretically, there may be possible additive cholinergic effects if huperzine A is taken with other anticholinesterase inhibitors or cholinergic agents.[14]

Synthesis[edit]

Two scalable and efficient total syntheses of huperzine A have been reported.[15][16]

See also[edit]

References[edit]

  1. ^ a b c 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, Biochemistry, and Behavior 75 (3): 675–86. doi:10.1016/S0091-3057(03)00111-4. PMID 12895686. 
  2. ^ Lim W, Goodger J, Field A, Holtum J, Woodrow I (2010). "Huperzine alkaloids from Australasian and southeast Asian Huperzia". Pharmaceutical biology 48 (9): 1073–8. doi:10.3109/13880209.2010.485619. PMID 20731560. 
  3. ^ a b Yang G, Wang Y, Tian J, Liu J (2013). "Huperzine A for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials". PLoS ONE 8 (9): e74916. doi:10.1371/journal.pone.0074916. PMC 3781107. PMID 24086396. 
  4. ^ a b Li J, Wu H, Zhou R, Liu G, Dong B (16 Apr 2008). "Huperzine A for Alzheimer’s disease". Cochrane Database Syst Rev (2): CD005592. doi:10.1002/14651858.CD005592.pub2. PMID 18425924. 
  5. ^ Wang B, Wang H, Wei Z, Song Y, Zhang L, Chen H (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. ^ Tang X, He X, Bai D (1999). "Huperzine A: A novel acetylcholinesterase inhibitor". Drugs of the Future 24 (6): 647. doi:10.1358/dof.1999.024.06.545143. 
  7. ^ Coleman B, Ratcliffe R, Oguntayo S, Shi X, Doctor B, Gordon R, Nambiar M (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. 
  8. ^ Patocka J (1998). "Huperzine A--an interesting anticholinesterase compound from the Chinese herbal medicine". Acta Medica (Hradec Kralove) 41 (4): 155–7. PMID 9951045. 
  9. ^ Raves M, Harel M, Pang Y, Silman I, Kozikowski A, Sussman J (1997). "Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A". Nature Structural Biology 4 (1): 57–63. doi:10.1038/nsb0197-57. PMID 8989325. 
  10. ^ Bai D, Tang X, He X (2000). "Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease". Current medicinal chemistry 7 (3): 355–74. doi:10.2174/0929867003375281. PMID 10637369. 
  11. ^ Talbott, SM (2012). Huperzine A (HupA). A Guide to Understanding Dietary Supplements (Routledge). pp. 304–. ISBN 978-1-136-80570-7. 
  12. ^ a b Pepping J (15 Mar 2000). "Huperzine A". Am J Health Syst Pharm 57 (6): 530, 533–4. PMID 10754762. 
  13. ^ "Huperzine A". Natural Standard: The Authority on Integrative Medicine. Natural Standard. Retrieved 29 October 2014. 
  14. ^ Skolnick A (12 Mar 1997). "Old Chinese herbal medicine used for fever yields possible new Alzheimer Disease therapy". JAMA 277 (10): 776. PMID 9052690. 
  15. ^ Tun MK, Wüstmann D, Herzon SB (2011). "A robust and scalable synthesis of the potent neuroprotective agent (−)-huperzine A". Chemical Science 2 (11): 2251. doi:10.1039/C1SC00455G. 
  16. ^ Tudhope SR, Bellamy JA, Ball A, Rajasekar D, Azadi-Ardakani M, Meera HS, Gnanadeepam JM, Saiganesh R, Gibson F, He L, Behrens CH, Underiner G, Marfurt J, Favre N (2012). "Development of a Large-Scale Synthetic Route to Manufacture (−)-Huperzine A". Organic Process Research & Development 16 (4): 635. doi:10.1021/op200360b.