Huperzine A

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Huperzine A
Huperzine A.png
HuperzineA3d.png
Clinical data
Other namesHupA
Routes of
administration		Oral
ATC code
Pharmacokinetic data
Elimination half-life10-14h[1]
Identifiers
  • (1R,9R,13E)-1-Amino-13-ethylidene-11-methyl-6-azatricyclo[7.3.1.02,7]trideca-2(7),3,10-trien-5-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.132.430 Edit this at Wikidata
Chemical and physical data
FormulaC15H18N2O
Molar mass242.322 g·mol−1
3D model (JSmol)
Melting point217 to 219 °C (423 to 426 °F)
  • C/C=C/1\[C@@H]2CC3=C([C@]1(CC(=C2)C)N)C=CC(=O)N3
InChI
  • 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
 ☒NcheckY (what is this?)  

Huperzine A is a naturally occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata[2] and in varying quantities in other food Huperzia species, including H. elmeri, H. carinat, and H. aqualupian.[3] Huperzine A has been investigated as a treatment for neurological conditions such as Alzheimer's disease, but a meta-analysis of those studies concluded that they were of poor methodological quality and the findings should be interpreted with caution.[4][5] Huperzine A inhibits the breakdown of the neurotransmitter acetylcholine by the enzyme acetylcholinesterase. It is commonly available over the counter as a nutrient supplement, and is marketed as a cognitive enhancer for improving memory and concentration.

Pharmacological effects[]

Huperzine A is extracted from Huperzia serrata.[2] It is a reversible acetylcholinesterase inhibitor[6][7][8][9] and NMDA receptor antagonist[10] that crosses the blood-brain barrier.[11] Acetylcholinesterase is an enzyme that catalyzes the breakdown of the neurotransmitter acetylcholine and of some other choline esters that function as neurotransmitters. The structure of the complex of huperzine A with acetylcholinesterase has been determined by X-ray crystallography (PDB code: 1VOT; see the 3D structure).[12]

For some years, huperzine A has been investigated as a possible treatment for diseases characterized by neurodegeneration, particularly Alzheimer's disease.[2][13] 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 unless further high quality studies confirm its beneficial effects.[4]

Huperzine A is also marketed as a dietary supplement with claims made for its ability to improve memory and mental function.[14]

Huperzine A has also been noted to help induce lucid dreaming.[15]

Adverse effects[]

Huperzine A may present with mild cholinergic side effects such as nausea, vomiting, and diarrhea.[5] Slight muscle twitching and slurred speech might also occur, as well as excessive saliva excretion and sweating. The use of huperzine A during pregnancy and lactation is not recommended due to the lack of sufficient safety data.[16]

Drug interactions[]

Huperzine A may have additive effects if taken with drugs causing bradycardia, such as beta-blockers,[17] which may decrease heart rate. Theoretically, there may be possible additive cholinergic effects if huperzine A is taken with other acetylcholinesterase inhibitors or cholinergic agents.[18]

Safety[]

Huperzine A, in spite of the possible cholinergic side effects, seems to have a wide margin of safety. Toxicology studies show Huperzine A to be non-toxic even when administered at 50-100 times the human therapeutic dose. The extract is active for 6 hours at a dose of 2 μg/kg with no remarkable side effects. [19]

Other possible uses[]

Huperzine A might be useful in the treatment of organophosphate nerve agent poisoning, preventing damage to the central nervous system caused by such agents. [20] [21]

Synthesis[]

Two scalable and efficient total syntheses of huperzine A have been reported.[22][23]

References[]

  1. ^ Li YX, Zhang RQ, Li CR, Jiang XH (2007). "Pharmacokinetics of huperzine A following oral administration to human volunteers". European Journal of Drug Metabolism and Pharmacokinetics. 32 (4): 183–187. doi:10.1007/BF03191002. PMID 18348466. S2CID 2702029.
  2. ^ 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): 675–686. doi:10.1016/S0091-3057(03)00111-4. PMID 12895686. S2CID 36435892.
  3. ^ Lim WH, Goodger JQ, Field AR, Holtum JA, Woodrow IE (2010). "Huperzine alkaloids from Australasian and southeast Asian Huperzia". Pharmaceutical Biology. 48 (9): 1073–1078. doi:10.3109/13880209.2010.485619. PMID 20731560.
  4. ^ 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. Bibcode:2013PLoSO...874916Y. doi:10.1371/journal.pone.0074916. PMC 3781107. PMID 24086396.
  5. ^ a b Li J, Wu HM, Zhou RL, Liu GJ, Dong BR (16 April 2008). "Huperzine A for Alzheimer's disease". Cochrane Database of Systematic Reviews. CD005592 (2): CD005592. doi:10.1002/14651858.CD005592.pub2. PMID 18425924.
  6. ^ Wang, R; Yan, H; Tang, XC (January 2006). "Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine". Acta Pharmacologica Sinica. 27 (1): 1–26. doi:10.1111/j.1745-7254.2006.00255.x. PMID 16364207. Retrieved 6 December 2017. Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE).
  7. ^ Meletis, Chris D.; Jason E. Barke (2004). Herbs and Nutrients for the Mind: A Guide to Natural Brain Enhancers. Greenwood Publishing Group. p. 191. ISBN 978-0275983949.
  8. ^ 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. 116 (4): 457–465. doi:10.1007/s00702-009-0189-x. PMID 19221692. S2CID 8655284.
  9. ^ 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.
  10. ^ 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): 387–395. doi:10.1016/j.cbi.2008.05.023. PMID 18588864.
  11. ^ Patocka J (1998). "Huperzine A - an interesting anticholinesterase compound from the Chinese herbal medicine" (PDF). Acta Medica. 41 (4): 155–7. doi:10.14712/18059694.2019.181. PMID 9951045.
  12. ^ Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL (1997). "Structure of acetylcholinesterase complexed with the nootropic alkaloid, (–)-huperzine A". Nature Structural & Molecular Biology. 4 (1): 57–63. doi:10.1038/nsb0197-57. PMID 8989325. S2CID 236518.
  13. ^ Bai DL, Tang XC, He XC (2000). "Huperzine A, A Potential Therapeutic Agent for Treatment of Alzheimer's Disease". Current Medicinal Chemistry. 7 (3): 355–374. doi:10.2174/0929867003375281. PMID 10637369.
  14. ^ Talbott, SM (2012). Huperzine A (HupA). A Guide to Understanding Dietary Supplements. Routledge. pp. 304–. ISBN 978-1-136-80570-7.
  15. ^ "Lucid Dreaming: A Beginner's Guide". The Four Hour Work Week. 22 September 2009. Retrieved 29 December 2016.
  16. ^ "Huperzine A". Natural Standard: The Authority on Integrative Medicine. Natural Standard. Retrieved 29 October 2014.
  17. ^ Pepping J (1 March 2000). "Huperzine A". American Journal of Health-System Pharmacy. 57 (6): 530, 533–534. doi:10.1093/ajhp/57.6.530. PMID 10754762.
  18. ^ Skolnick AA (12 March 1997). "Old Chinese Herbal Medicine Used for Fever Yields Possible New Alzheimer Disease Therapy". JAMA. 277 (10): 776. doi:10.1001/jama.1997.03540340010004. PMID 9052690.
  19. ^ Lallement, G.; Baille, V.; Baubichon, D.; Carpentier, P.; Collombet, J. M.; Filliat, P.; Foquin, A.; Four, E.; Masqueliez, C.; Testylier, G.; Tonduli, L.; Dorandeu, F. (May 2002). "Huperzine-A". Neurotoxicology. 23 (1): 1–5. doi:10.1016/S0161-813X(02)00015-3. PMID 12164543.
  20. ^ "Review of the Value of Huperzine as Pretreatment of Organophosphate Poisoning". Nutrition Review. 22 April 2013.
  21. ^ Liu, L.; Sun, J. X. (2005). "Advances on study of organophosphate poisoning prevented by Huperzine A". Wei Sheng Yan Jiu = Journal of Hygiene Research. 34 (2): 224–226. PMID 15952670.
  22. ^ Tun MK, Wüstmann D, Herzon SB (2011). "A robust and scalable synthesis of the potent neuroprotective agent (−)-huperzine A". Chemical Science. 2 (11): 2251–2253. doi:10.1039/C1SC00455G. S2CID 98224866.
  23. ^ 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): 635–642. doi:10.1021/op200360b.

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