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Identification
NameHuperzine A
Accession NumberDB04864  (EXPT01795, DB01928)
TypeSmall Molecule
GroupsInvestigational
Description

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. [Wikipedia]

Structure
Thumb
Synonyms
(−)-huperazine A
(−)-selagine
L-huperzine A
selagine
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0111871I23
CAS number102518-79-6
WeightAverage: 242.3162
Monoisotopic: 242.141913208
Chemical FormulaC15H18N2O
InChI KeyZRJBHWIHUMBLCN-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[7.3.1.0²,⁷]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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinolones and derivatives
Direct ParentQuinolones and derivatives
Alternative Parents
Substituents
  • Quinolone
  • Aralkylamine
  • Pyridinone
  • Pyridine
  • Heteroaromatic compound
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of Alzheimer's disease.
PharmacodynamicsHuperzine 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 actionHuperzine 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9809
Blood Brain Barrier+0.9053
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.6843
P-glycoprotein inhibitor INon-inhibitor0.7767
P-glycoprotein inhibitor IINon-inhibitor0.7828
Renal organic cation transporterNon-inhibitor0.82
CYP450 2C9 substrateNon-substrate0.8177
CYP450 2D6 substrateNon-substrate0.8258
CYP450 3A4 substrateSubstrate0.6804
CYP450 1A2 substrateInhibitor0.5759
CYP450 2C9 inhibitorInhibitor0.6166
CYP450 2D6 inhibitorNon-inhibitor0.7873
CYP450 2C19 inhibitorInhibitor0.5397
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8312
Ames testNon AMES toxic0.6062
CarcinogenicityNon-carcinogens0.9234
BiodegradationNot ready biodegradable0.9967
Rat acute toxicity3.5096 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.993
hERG inhibition (predictor II)Non-inhibitor0.6042
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point217-219 °CNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.166 mg/mLALOGPS
logP1.78ALOGPS
logP0.62ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)11.11ChemAxon
pKa (Strongest Basic)9.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area55.12 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity75.79 m3·mol-1ChemAxon
Polarizability26.87 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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. [PubMed:17908041 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Molecular Weight:
67795.525 Da
References
  1. 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. [PubMed:12895686 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Molecular Weight:
67795.525 Da
References
  1. 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. [PubMed:10592235 ]
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Drug created on October 19, 2007 17:03 / Updated on August 17, 2016 12:24