Identification

Name
Huperzine A
Accession Number
DB04864  (EXPT01795, DB01928, DB05510)
Type
Small Molecule
Groups
Approved, Experimental
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.

Structure
Thumb
Synonyms
  • (−)-huperazine A
  • (−)-selagine
  • Huperzine-A
  • L-huperzine A
  • Selagine
Categories
UNII
0111871I23
CAS number
102518-79-6
Weight
Average: 242.3162
Monoisotopic: 242.141913208
Chemical Formula
C15H18N2O
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[7.3.1.0²,⁷]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

Pharmacology

Indication

Investigated for use/treatment in alzheimer's disease.

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.

TargetActionsOrganism
UAcetylcholinesterase
inhibitor
Human
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Huperzine A.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Huperzine A.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Huperzine A.
AcebutololHuperzine A may increase the bradycardic activities of Acebutolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Huperzine A is combined with Acetylcholine.
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Huperzine A.
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Huperzine A.
AlclometasoneThe therapeutic efficacy of Huperzine A can be decreased when used in combination with Alclometasone.
AlcuroniumThe therapeutic efficacy of Alcuronium can be decreased when used in combination with Huperzine A.
AldosteroneThe risk or severity of adverse effects can be increased when Aldosterone is combined with Huperzine A.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:18230054]
  2. 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]
  3. 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. [PubMed:17305579]
  4. 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. [PubMed:16634467]
  5. 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. [PubMed:16364207]
  6. 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. [PubMed:15956816]
  7. Authors unspecified: Huperzine A. Drugs R D. 2004;5(1):44-5. [PubMed:14725492]
  8. 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. [PubMed:14529340]
  9. 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]
External Links
KEGG Compound
C09992
PubChem Compound
854026
PubChem Substance
175426873
ChemSpider
16736021
BindingDB
50199522
ChEBI
78330
ChEMBL
CHEMBL395280
HET
HUP
Wikipedia
Huperzine_A
PDB Entries
1gpk / 1vot / 4ey5

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableCocaine Abuse / Dependence, Cocaine / Substance Abuse1
1CompletedTreatmentEpilepsy, Complex Partial1
1, 2RecruitingTreatmentFocal Impaired Awareness Seizures1
2CompletedTreatmentAlzheimer's Disease (AD)1
2RecruitingTreatmentTraumatic Brain Injury (TBI)1
2, 3Unknown StatusPreventionAlzheimer's Disease (AD)1
4Not Yet RecruitingPreventionBiomarkers / Diagnosis / Mild Cognitive Impairment (MCI) / Treatments1
4Unknown StatusTreatmentDementias / Schizophrenic Disorders1
Not AvailableCompletedNot AvailableBiomarkers, Pharmacological1
Not AvailableEnrolling by InvitationTreatmentCognitive Impairments / Presbyacusis / Tinnitus1
Not AvailableUnknown StatusTreatmentBioavailability / Healthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)217-219 °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
Refractivity75.8 m3·mol-1ChemAxon
Polarizability26.87 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Quinolone / Pyridinone / Aralkylamine / Pyridine / Heteroaromatic compound / Lactam / Azacycle / Amine / Hydrocarbon derivative / Organic oxide
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organic heterotricyclic compound, primary amino compound, pyridone, sesquiterpene alkaloid (CHEBI:78330)

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Human
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
  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]
  2. 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]

Drug created on October 19, 2007 17:03 / Updated on October 08, 2018 21:32