Huperzine A, aLycopodiumalkaloid, was first isolated in 1983 fromHuperzia serrata,[2][3][4] a plant used in Chinese folk medicine. Huperzine A also exists in other Huperzia species, includingH. elmeri,H. carinat, andH. aqualupian with varying quantities.[5]
Huperzine A has been investigated as a treatment for neurological conditions such asAlzheimer's disease, but a 2013meta-analysis of those studies concluded that they were of poor methodological quality and the findings should be interpreted with caution.[6][7] Huperzine A inhibits the breakdown of theneurotransmitteracetylcholine (ACh) by the enzymeacetylcholinesterase. It is also an antagonist of theNMDA receptor. It is commonly available over the counter as anutritional supplement and marketed as a memory and concentrationenhancer.
Huperzine A may present with mildcholinergic side effects such as nausea, vomiting, and diarrhea.[7] Slight muscle twitching and slurred speech might also occur, as well ashypersalivation and sweating. The use of huperzine A during pregnancy and lactation is not recommended due to the lack of sufficient safety data.[8]
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.[18]
In 1989, a research study found[21] that the chemical structure of the alkaloid selagine reported in 1960 from a study ofLycopodium slago L.[22] (analyzed using 60-MHzNMR) was identical to that of Huperzine A.
Huperzine A has been investigated as a possible treatment for diseases characterized byneurodegeneration such asAlzheimer's disease,[23][24] and there is some evidence from small-scale studies that it can benefit cognitive functioning, global clinical status, and ability to engage inactivities of daily living (ADLs) among individuals with the disease. In a 2016systematic review of systematic reviews,[25] huperzine A was associated with astandardized 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,[26] huperzine A was associated with broad benefits to dementia patients' cognitive functioning, but the degree ofheterogeneity in measurements and outcomes of the reviewed studies indicatedpublication bias toward huperzine A benefit.
^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.PMID18348466.S2CID2702029.
^Liu JS, Zhu YL, Yu CM, Zhou YZ, Han YY, Wu FW, et al. (1986). "The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity".Canadian Journal of Chemistry.64 (4):837–839.Bibcode:1986CaJCh..64..837L.doi:10.1139/v86-137.
^US 5,177,082, Yu CM, Tang XC, Liu JS, Han YY, "Huperzines and analogs.", issued 5 January 1993
^Yu CM, Calhoun LA, Konder RM, Grant AS (2014). "Huperzimine, a novel Lycopodium alkaloid from Huperzia serrata".Canadian Journal of Chemistry.92 (5):406–410.Bibcode:2014CaJCh..92..406Y.doi:10.1139/cjc-2013-0520.
^Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ (April 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.PMID19221692.S2CID8655284.
^Tang XC, He XC, Bai DL (1999). "Huperzine A: A novel acetylcholinesterase inhibitor".Drugs of the Future.24 (6): 647.doi:10.1358/dof.1999.024.06.545143.
^Coleman BR, Ratcliffe RH, Oguntayo SA, Shi X, Doctor BP, Gordon RK, et al. (September 2008). "[+]-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats".Chemico-Biological Interactions.175 (1–3):387–395.Bibcode:2008CBI...175..387C.doi:10.1016/j.cbi.2008.05.023.PMID18588864.
^Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL (January 1997). "Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A".Nature Structural Biology.4 (1):57–63.doi:10.1038/nsb0197-57.PMID8989325.S2CID236518.
^un MK, Wüstmann DJ, 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.S2CID98224866.
^Tudhope SR, Bellamy JA, Ball A, Rajasekar D, Azadi-Ardakani M, Meera HS, et al. (2012). "Development of a Large-Scale Synthetic Route to Manufacture (−)-Huperzine A".Organic Process Research & Development.16 (4):635–642.doi:10.1021/op200360b.
^Ayer WA, Browne LM, Orszanska H, Valenta Z (October 1989). "Alkaloids ofLycopodium selago. On the identity of selagine with huperzine A and the structure of a related alkaloid".Canadian Journal of Chemistry.67 (10):1538–1540.Bibcode:1989CaJCh..67.1538A.doi:10.1139/v89-234.
^Valenta Z, Yoshimura H, Rogers EF, Ternbah M, Wiesner K (January 1960). "The structure of selagine".Tetrahedron Letters.1 (31):26–33.doi:10.1016/S0040-4039(01)99300-1.
^Zangara A (June 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.PMID12895686.S2CID36435892.
^Bai DL, Tang XC, He XC (March 2000). "Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease".Current Medicinal Chemistry.7 (3):355–374.doi:10.2174/0929867003375281.PMID10637369.
^Fan F, Liu H, Shi X, Ai Y, Liu Q, Cheng Y (2022-02-01). "The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review".Journal of Alzheimer's Disease.85 (3):1195–1204.doi:10.3233/JAD-215423.PMID34924395.S2CID245311001.
^Lallement G, Baille V, Baubichon D, Carpentier P, Collombet JM, Filliat P, et al. (May 2002). "Review of the value of huperzine as pretreatment of organophosphate poisoning".Neurotoxicology.23 (1):1–5.doi:10.1016/s0161-813x(02)00015-3.PMID12164543.
N
Y (what is this?) (verify)