Huperzine A
Identification
- Generic Name
- Huperzine A
- DrugBank Accession Number
- DB04864
- Background
Huperzine A, is a naturally occurring sesquiterpene alkaloid found in the extracts of the firmoss Huperzia serrata. The botanical has been used in China for centuries for the treatment of swelling, fever and blood disorders. Recently in clinical trials in China, it has demonstrated neuroprotective effects. It is currently being investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer’s disease.
- Type
- Small Molecule
- Groups
- Approved, Experimental
- Structure
- Weight
- Average: 242.3162
Monoisotopic: 242.141913208 - Chemical Formula
- C15H18N2O
- Synonyms
- (−)-huperazine A
- (−)-selagine
- Huperzine-A
- L-huperzine A
- Selagine
Pharmacology
- Indication
Investigated for use/treatment in alzheimer's disease.
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- Pharmacodynamics
Huperzine A is an alkaloid derived from Huperzia serrata (which is available as an herbal product in the US). It is under investigation as an acetylcholinesterase inhibitor. Clinical trials in China have shown that huperzine A is comparably effective to the drugs currently on the market, and may even be somewhat safer in terms of side effects.
- Mechanism of action
Huperzine A has been found to be an inhibitor of the enzyme acetylcholinesterase. This is the same mechanism of action of pharmaceutical drugs such as galantamine and donepezil used to treat Alzheimer's disease.
Target Actions Organism UAcetylcholinesterase inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcebutolol Huperzine A may increase the bradycardic activities of Acebutolol. Acetylcholine The risk or severity of adverse effects can be increased when Huperzine A is combined with Acetylcholine. Aclidinium Huperzine A may increase the neuromuscular blocking activities of Aclidinium. Amantadine The therapeutic efficacy of Amantadine can be decreased when used in combination with Huperzine A. Amifampridine The risk or severity of adverse effects can be increased when Huperzine A is combined with Amifampridine. Amitriptyline The therapeutic efficacy of Amitriptyline can be decreased when used in combination with Huperzine A. Amobarbital The therapeutic efficacy of Amobarbital can be decreased when used in combination with Huperzine A. Amoxapine The therapeutic efficacy of Amoxapine can be decreased when used in combination with Huperzine A. Anisotropine methylbromide The therapeutic efficacy of Anisotropine methylbromide can be decreased when used in combination with Huperzine A. Aripiprazole The therapeutic efficacy of Aripiprazole can be decreased when used in combination with Huperzine A. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinolones and derivatives. These are compounds containing a quinoline moiety which bears a ketone group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Quinolones and derivatives
- Direct Parent
- Quinolones and derivatives
- Alternative Parents
- Pyridinones / Aralkylamines / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
- Substituents
- Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Lactam / Organic nitrogen compound / Organic oxide / Organic oxygen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organic heterotricyclic compound, primary amino compound, pyridone, sesquiterpene alkaloid (CHEBI:78330)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0111871I23
- CAS number
- 102518-79-6
- InChI Key
- ZRJBHWIHUMBLCN-YQEJDHNASA-N
- InChI
- 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
- IUPAC Name
- (1R,9R,13E)-1-amino-13-ethylidene-11-methyl-6-azatricyclo[7.3.1.0^{2,7}]trideca-2(7),3,10-trien-5-one
- SMILES
- [H][C@@]12CC3=C(C=CC(=O)N3)[C@@](N)(CC(C)=C1)\C2=C\C
References
- General References
- Little JT, Walsh S, Aisen PS: An update on huperzine A as a treatment for Alzheimer's disease. Expert Opin Investig Drugs. 2008 Feb;17(2):209-15. doi: 10.1517/13543784.17.2.209. [Article]
- Li WM, Kan KK, Carlier PR, Pang YP, Han YF: East meets West in the search for Alzheimer's therapeutics - novel dimeric inhibitors from tacrine and huperzine A. Curr Alzheimer Res. 2007 Sep;4(4):386-96. [Article]
- Haviv H, Wong DM, Silman I, Sussman JL: Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors. Curr Top Med Chem. 2007;7(4):375-87. [Article]
- Akhondzadeh S, Abbasi SH: Herbal medicine in the treatment of Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2006 Mar-Apr;21(2):113-8. [Article]
- Wang R, Yan H, Tang XC: Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006 Jan;27(1):1-26. [Article]
- Wang R, Tang XC: Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease. Neurosignals. 2005;14(1-2):71-82. [Article]
- Authors unspecified: Huperzine A. Drugs R D. 2004;5(1):44-5. [Article]
- Jiang H, Luo X, Bai D: Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer's disease. Curr Med Chem. 2003 Nov;10(21):2231-52. [Article]
- Zangara A: The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease. Pharmacol Biochem Behav. 2003 Jun;75(3):675-86. [Article]
- External Links
- KEGG Compound
- C09992
- PubChem Compound
- 854026
- PubChem Substance
- 175426873
- ChemSpider
- 16736021
- BindingDB
- 50199522
- 2267703
- ChEBI
- 78330
- ChEMBL
- CHEMBL395280
- ZINC
- ZINC000009411213
- PDBe Ligand
- HUP
- Wikipedia
- Huperzine_A
- PDB Entries
- 1gpk / 1vot / 4ey5
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Prevention Biomarkers / Diagnosis / Mild Cognitive Impairment (MCI) / Treatments 1 4 Not Yet Recruiting Treatment Postoperative Cognitive Dysfunction in Patients With Aneurysmal Subarachnoid Hemorrhage 1 4 Unknown Status Treatment Dementia / Schizophrenia 1 4 Unknown Status Treatment Sensory abnormalities NEC 1 2 Completed Treatment Alzheimer's Disease (AD) 1 2 Recruiting Treatment Epilepsies / Epileptic seizure 1 2 Terminated Treatment Traumatic Brain Injury (TBI) 1 2, 3 Unknown Status Prevention Alzheimer's Disease (AD) 1 1 Completed Not Available Cocaine Abuse / Dependence, Cocaine / Substance Abuse 1 1 Completed Treatment Focal Impaired Awareness Seizures 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 217-219 °C Not Available - Predicted Properties
Property Value Source Water Solubility 0.166 mg/mL ALOGPS logP 1.78 ALOGPS logP 0.62 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 11.11 Chemaxon pKa (Strongest Basic) 9.09 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 55.12 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 75.8 m3·mol-1 Chemaxon Polarizability 26.87 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9809 Blood Brain Barrier + 0.9053 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.6843 P-glycoprotein inhibitor I Non-inhibitor 0.7767 P-glycoprotein inhibitor II Non-inhibitor 0.7828 Renal organic cation transporter Non-inhibitor 0.82 CYP450 2C9 substrate Non-substrate 0.8177 CYP450 2D6 substrate Non-substrate 0.8258 CYP450 3A4 substrate Substrate 0.6804 CYP450 1A2 substrate Inhibitor 0.5759 CYP450 2C9 inhibitor Inhibitor 0.6166 CYP450 2D6 inhibitor Non-inhibitor 0.7873 CYP450 2C19 inhibitor Inhibitor 0.5397 CYP450 3A4 inhibitor Non-inhibitor 0.831 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8312 Ames test Non AMES toxic 0.6062 Carcinogenicity Non-carcinogens 0.9234 Biodegradation Not ready biodegradable 0.9967 Rat acute toxicity 3.5096 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.993 hERG inhibition (predictor II) Non-inhibitor 0.6042
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serine hydrolase activity
- Specific Function
- Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
- Gene Name
- ACHE
- Uniprot ID
- P22303
- Uniprot Name
- Acetylcholinesterase
- Molecular Weight
- 67795.525 Da
References
- Zangara A: The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease. Pharmacol Biochem Behav. 2003 Jun;75(3):675-86. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Drug created at October 19, 2007 23:03 / Updated at December 23, 2021 07:46