Clinical data | |
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Other names | HupA |
Routes of administration | Oral |
ATC code | |
Pharmacokinetic data | |
Elimination half-life | 10-14h [1] |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.132.430 |
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) |
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(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.
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.
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]
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]
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]
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]
Two scalable and efficient total syntheses of huperzine A have been reported. [22] [23]
Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE).
Clinical data | |
---|---|
Other names | HupA |
Routes of administration | Oral |
ATC code | |
Pharmacokinetic data | |
Elimination half-life | 10-14h [1] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.132.430 |
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) |
| |
| |
(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.
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.
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]
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]
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]
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]
Two scalable and efficient total syntheses of huperzine A have been reported. [22] [23]
Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE).