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-life 10-14h [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 InfoCard 100.132.430 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H18N2O
Molar mass 242.322 g·mol−1
3D model (JSmol)
Melting point 217 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 Yes check.svgY
  • Key:ZRJBHWIHUMBLCN-YQEJDHNASA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 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 also an antagonist of the NMDA-receptor. It is commonly available over the counter as a nutritional supplement and marketed as a memory and concentration enhancer.

Contents

Huperzine A has also been noted to help induce lucid dreaming. [6]

Pharmacological effects

Huperzine A is extracted from Huperzia serrata . [2] It is a reversible acetylcholinesterase inhibitor [7] [8] [9] [10] and NMDA receptor antagonist [11] that crosses the blood–brain barrier. [12] 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). [13]

Huperzine A has been investigated as a possible treatment for diseases characterized by neurodegeneration such as Alzheimer's disease, [2] [14] 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, [15] 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, [16] 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. [17]

Drug interactions

Huperzine A may have additive effects if taken with drugs causing bradycardia, such as beta-blockers, [18] 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. [19]

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. [20]

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. [21] [22]

Synthesis

Two scalable and efficient total syntheses of huperzine A have been reported. [23] [24]

Related Research Articles

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Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.

<span class="mw-page-title-main">Cholinergic</span> Agent which mimics choline

Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells.

<span class="mw-page-title-main">Cholinesterase</span> Esterase that lyses choline-based esters

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<span class="mw-page-title-main">Azinphos-methyl</span> Chemical compound

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References

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