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Huperzine A
Natural API
Huperzine A.jpg
huperzia.jpg

Huperzine A

Huperzine A is a natural alkaloid​isolated from the Chinese medicinal herb Huperzia serrata (Lycopodiaceae family). As a highly selective acetylcholinesterase (AChE) inhibitor, it is widely used for treating Alzheimer’s disease (AD)​and cognitive impairment. Additionally, Huperzine A exhibits neuroprotective, antioxidant, and anti-inflammatory​ properties, making it a key focus in natural drug research.

Product Name: Huperzine A

IUPAC Name: (5R,9R,11E)-5-Amino-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one

CAS No.​: 102518-79-6

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    Huperzine A

    Basic information

    Product Name: Huperzine A

    IUPAC Name: (5R,9R,11E)-5-Amino-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one

    CAS No.​: 102518-79-6

    Molecular Formula: C₁₅H₁₈N₂O

    Physicochemical Properties:

    Parameter

    Value/Description

    ​Appearance​

    White to off-white crystalline powder

    ​Melting Point​

    230-232°C (decomposition)

    ​Solubility​

    Slightly soluble in water (0.1 mg/mL), soluble in DMSO (>50 mg/mL)

    ​logP​

    2.5 (moderate lipophilicity)

    ​Stability​

    Light-sensitive; stable at pH <4

    Quality Standard: CP2020,JP,Customer Made

    Specification

    Test Items

    Standard

    Huperzine A (CAS: 102518-79-6)

    98% by HPLC

    Loss on drying

    ≤4.0%

    Residue on ignition

    ≤1.0%

    Key Features

    index_10-7

    Natural Source

    Found in Huperzia serrata (0.01%-0.1% content), also obtainable via ​chemical synthesis​ or ​microbial fermentation.
    index_10-7

    High Selectivity

    Strong AChE inhibition (IC₅₀=82 nM) with minimal effect on butyrylcholinesterase (BuChE, IC₅₀=74 μM).
    index_10-7

    Multi-Target Action

     Beyond AChE inhibition, it modulates ​NMDA receptors, ​reduces oxidative stress, and ​inhibits apoptosis.

    Pharmacological Mechanisms

    1.Molecular Mechanism

    Pharmacological Mechanisms

    2.Pharmacokinetics

    Absorption

    Oral bioavailability ​~60%​​ (affected by first-pass metabolism).

    Distribution

    Easily crosses the BBB (brain/plasma ratio=2:1).

    Metabolism

    Primarily metabolized by ​CYP3A4​ into ​norhuperzine A.

    Excretion

    60% renal excretion; half-life ​~10 hours.

    Clinical Applications​

    Indications & Protocols​

    ​Condition​

    ​Dosage​

    ​Clinical Evidence​

    ​Alzheimer’s Disease​

    0.1-0.2 mg bid

    ↑MMSE score by 3-4 points

    ​Vascular Dementia​

    0.1 mg tid

    Improves ADAS-cog score

    ​Mild Cognitive Impairment​

    0.05 mg/day

    Delays AD progression

    Special Populations​

    Hepatic Impairment: Dose adjustment needed (CYP3A4 metabolism slowed).

    Elderly: Start with half dose (0.05 mg/day).

    Dosage and Administration

    Formulations​

    Tablets: 0.1 mg/tablet (Chinese Pharmacopoeia standard).

    Injection: 0.2 mg/mL (research use).

    Dosing Guidelines

    Indication​

    ​Dose​

    ​Duration​

    ​AD Treatment​

    0.1-0.2 mg bid

    Long-term

    ​Cognitive Enhancement​

    0.05-0.1 mg/day

    3-6 months

    Safety Evaluation

    Adverse Reactions​

    ​System​

    ​Incidence​

    ​Symptoms​

    ​Gastrointestinal​

    10%

    Nausea, diarrhea

    ​Neurological​

    5%

    Dizziness, insomnia

    ​Cholinergic Effects​

    3%

    Increased salivation

    Contraindications & Interactions​

    Absolute CI:
    Myasthenia gravis​ (risk of cholinergic crisis).
    Epilepsy​ (NMDA modulation may trigger seizures).

    Drug Interactions:
    CYP3A4 inhibitors (e.g., ketoconazole)​: ↑ Plasma concentration.
    Anticholinergics (e.g., atropine)​: Antagonistic effects.

    Research Progress Green max

    Novel Formulations​

    CYP3A4 inhibitors (e.g., ketoconazole)​: ↑ Plasma concentration.

    Anticholinergics (e.g., atropine)​: Antagonistic effects.

    New Indications

    Parkinson’s Disease: Modulates dopaminergic neurons (effective in animal models).

    Traumatic Brain Injury (TBI)​: Reduces neuroinflammation (Phase II trials).

    huperzia

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