Huperzine A

Source: Wikipedia, the free encyclopedia.
Huperzine A
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
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=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?)  (verify)

Huperzine A is a naturally-occurring

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 2013 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 (ACh) by the enzyme acetylcholinesterase. It is commonly available over the counter as a nutritional supplement and marketed as a memory and concentration enhancer
.

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 ACh and 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]

Huperzine A has been investigated as a possible treatment for diseases characterized by neurodegeneration such as Alzheimer's disease,[2][13] and there is some evidence from small-scale studies that it can benefit cognitive functioning, global clinical status, and ability to engage in activities of daily living (ADLs) among individuals with the disease. In a 2016 systematic review of systematic reviews,[14] huperzine A was associated with a standardized mean difference of 1.48 (95% CI, 0.95-2.02) compared to placebo on measures of ADL among people with dementia, but the evidence was very low-quality and uncertain. In a 2022 umbrella review,[15] huperzine A was associated with broad benefits to dementia patients' cognitive functioning, but the degree of heterogeneity in measurements and outcomes of the reviewed studies indicated publication bias toward huperzine A benefit.

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

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 by 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. S2CID 2702029
    .
  2. ^
    S2CID 36435892
    .
  3. PMID 20731560
    .
  4. PMID 24086396
    .
  5. ^
    PMID 18425924
    .
  6. PMID 16364207
    . 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. ISBN 978-0-275-98394-9
    .
  8. S2CID 8655284
    .
  9. doi:10.1358/dof.1999.024.06.545143
    .
  10. PMID 18588864
    .
  11. PMID 9951045
    .
  12. S2CID 236518
    .
  13. PMID 10637369
    .
  14. PMID 27121704
    .
  15. S2CID 245311001
    .
  16. ^ "Huperzine A". Natural Standard: The Authority on Integrative Medicine. Natural Standard. Retrieved 29 October 2014.
  17. PMID 10754762
    .
  18. PMID 9052690
    .
  19. PMID 12164543
    .
  20. ^ "Review of the Value of Huperzine as Pretreatment of Organophosphate Poisoning". Nutrition Review. 22 April 2013.
  21. PMID 15952670
    .
  22. S2CID 98224866
    .
  23. doi:10.1021/op200360b
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Huperzine_A&oldid=1216495768"