Huperzine A

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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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Huperzine A (DB04864)

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Weight

Average: 242.3162
Monoisotopic: 242.141913208

Chemical Formula

C₁₅H₁₈N₂O

Synonyms

• (-)-Huperzine A
• (−)-huperazine A
• (−)-selagine
• Huperzine-A
• L-huperzine A
• Selagine

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Pharmacology

Indication

Investigated for use/treatment in alzheimer's disease.

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Contraindications & Blackbox Warnings

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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
AAcetylcholinesterase	inhibitor	Humans

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

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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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Acebutolol	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.

Food Interactions

Not Available

Categories

Drug Categories

• Central Nervous System Agents
• Cholinergic Agents
• Cholinesterase Inhibitors
• Compounds used in a research, industrial, or household setting
• Enzyme Inhibitors
• Neuroprotective Agents
• Neurotransmitter Agents
• Protective Agents
• Terpenes

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

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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
7. Authors unspecified: Huperzine A. Drugs R D. 2004;5(1):44-5. [Article]
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. [Article]
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. [Article]

External Links

KEGG Compound

C09992

PubChem Compound

854026

PubChem Substance

175426873

ChemSpider

16736021

BindingDB

50199522

RxNav

2267703

ChEBI

78330

ChEMBL

CHEMBL395280

ZINC

ZINC000009411213

PDBe Ligand

HUP

Wikipedia

Huperzine_A

PDB Entries

1gpk / 1vot / 4ey5

Clinical Trials

Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
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4	Not Yet Recruiting	Prevention	Biomarkers / Diagnosis / Mild Cognitive Impairment (MCI) / Treatments	1	somestatus	stop reason	just information to hide
4	Not Yet Recruiting	Treatment	Postoperative Cognitive Dysfunction in Patients With Aneurysmal Subarachnoid Hemorrhage	1	somestatus	stop reason	just information to hide
4	Unknown Status	Treatment	Dementia / Schizophrenia	1	somestatus	stop reason	just information to hide
4	Unknown Status	Treatment	Sensory abnormalities NEC	1	somestatus	stop reason	just information to hide
2	Completed	Treatment	Alzheimer's Disease (AD)	1	somestatus	stop reason	just information to hide

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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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-002f-0090000000-2f78dc4c31f5bad0f847
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-0090000000-a2fdb7a5a30672caf410
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-004i-0290000000-976f0d43190f1b0f7e51
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-0190000000-f01548b6ea6a5a2fddeb
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-052p-3950000000-800503f9eb83bee81af8
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-005j-0920000000-c3558d353e140fde0cc0
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	163.513167	predicted	DarkChem Lite v0.1.0
[M-H]-	162.428567	predicted	DarkChem Lite v0.1.0
[M-H]-	159.80223	predicted	DeepCCS 1.0 (2019)
[M+H]+	163.994167	predicted	DarkChem Lite v0.1.0
[M+H]+	162.625767	predicted	DarkChem Lite v0.1.0
[M+H]+	162.1978	predicted	DeepCCS 1.0 (2019)
[M+Na]+	163.668167	predicted	DarkChem Lite v0.1.0
[M+Na]+	168.43954	predicted	DeepCCS 1.0 (2019)

Targets

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Binding Properties

×

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	260	N/A	N/A	A27977 / A29758 / A27993
IC 50 (nM)	47	N/A	N/A	A27987
IC 50 (nM)	21	N/A	N/A	A28007
IC 50 (nM)	1700	N/A	N/A	A28787
IC 50 (nM)	45	N/A	N/A	A29759
IC 50 (nM)	5	N/A	N/A	A18427 / A28014
IC 50 (nM)	150	N/A	N/A	A18427
IC 50 (nM)	47	8	37	A27981 / A27991
IC 50 (nM)	260	8	25	A30361
IC 50 (nM)	12	N/A	N/A	A28791
Ki (nM)	47	8	25	A27992

Details

Binding Properties1. Acetylcholinesterase

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis

Specific Function

Acetylcholine binding

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. [Article]
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. [Article]
3. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

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Drug created at October 19, 2007 23:03 / Updated at August 26, 2024 19:24