HUPERZINE A MONOHYDRATE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H18N2O.H2O
Molecular Weight	260.3315
Optical Activity	( - )
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.C\C=C1/[C@@H]2CC3=C(C=CC(=O)N3)[C@@]1(N)CC(C)=C2

InChI

InChIKey=JGPPGMFEKUOWLB-NSBUTGITSA-N

InChI=1S/C15H18N2O.H2O/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);1H2/b11-3+;/t10-,15+;/m0./s1

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C15H18N2O
Molecular Weight	242.3162
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	1
Optical Activity	( - )

Description
Sources: https://doi.org/10.1016/j.jalz.2009.05.218 | https://adisinsight.springer.com/drugs/800016260http://www.webmd.com/vitamins-supplements/ingredientmono-764-huperzine%20a.aspx
Curator's Comment: description was created based on several sources, including: https://www.braintropic.com/nootropics/huperzine-a/ | https://www.drugs.com/npc/huperzine-a.html | http://medind.nic.in/daa/t11/i1/daat11i1p177.pdf

Huperzine A is a plant alkaloid derived from Club moss plant, Huperzine serrata, which is a member or the Lycopodium species. Huperzine-A is in phase III clinical trial in the USA (Alzheimer disease) and is available as a dietary supplement. It selectively and reversibly inhibits acetylcholinesterase. Huperzine A is also a NMDA receptor antagonist, which protects the brain against glutamate induced damage, and it increases nerve growth factor levels. Huperzine A is used for Alzheimer's disease, memory and learning enhancement, and age-related memory impairment. It is also used for treating a muscle disease called myasthenia gravis, for increasing alertness and energy, and for protecting against agents that damage the nerves such as nerve gases. It can cause some side effects including nausea, diarrhea, vomiting, sweating, blurred vision, slurred speech, restlessness, loss of appetite, contraction and twitching of muscle fibers, cramping, increased saliva and urine, inability to control urination, high blood pressure, and slowed heart rate. Various medications used for glaucoma, Alzheimer's disease, and other conditions (Cholinergic drugs) interacts with Huperzine A.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10375798	Inhibitor 8504		64.7 nM [IC50]
Glutamate NMDA receptor 47 Target ID: CHEMBL1907608 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10437121	Antagonist 2849		0.5 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 278 Sources: https://nutritionreview.org/2013/04/huperzinea/ https://www.ncbi.nlm.nih.gov/pubmed/19221692	Primary	Phase III 665	Unknown Approved Use Unknown
Schizophrenia 305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27302211	Palliative	Phase IV 63	Unknown Approved Use Unknown
Age-related memory impairment 4 Sources: http://www.webmd.com/vitamins-supplements/ingredientmono-764-huperzine%20a.aspx	Primary	Approved 8583	Huperzine A Approved Use Huperzine A can be used as a memory enhancer. It can also be taken regularly to help protect against age-related declines in memory.

C_max

Value	Dose	Co-administered	Analyte	Population
2.59 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18348466/	0.4 mg single, oral dose: 0.4 mg route of administration: Oral experiment type: SINGLE co-administered:		HUPERZINE A plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2450.34 μg × min/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18348466/	0.4 mg single, oral dose: 0.4 mg route of administration: Oral experiment type: SINGLE co-administered:		HUPERZINE A plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
716.25 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18348466/	0.4 mg single, oral dose: 0.4 mg route of administration: Oral experiment type: SINGLE co-administered:		HUPERZINE A plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.4 mg 2 times / day multiple, oral Highest studied dose Dose: 0.4 mg, 2 times / day Route: oral Route: multiple Dose: 0.4 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26364275/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26364275/	Sources: https://pubmed.ncbi.nlm.nih.gov/26364275/
600 ug 1 times / day multiple, oral Highest studied dose\|Studied dose Dose: 600 ug, 1 times / day Route: oral Route: multiple Dose: 600 ug, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/results/NCT01676311?term=HUPERZINE+A&rslt=With&draw=2&rank=1 https://pubmed.ncbi.nlm.nih.gov/31638455/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT01676311?term=HUPERZINE+A&rslt=With&draw=2&rank=1 https://pubmed.ncbi.nlm.nih.gov/31638455/	Other AEs: Seizure... Other AEs: Seizure (serious, 28.6%) Sources: https://clinicaltrials.gov/ct2/show/results/NCT01676311?term=HUPERZINE+A&rslt=With&draw=2&rank=1 https://pubmed.ncbi.nlm.nih.gov/31638455/
0.1 mg 2 times / day steady, oral Studied dose Dose: 0.1 mg, 2 times / day Route: oral Route: steady Dose: 0.1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21833673/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21833673/	Sources: https://pubmed.ncbi.nlm.nih.gov/21833673/
0.2 mg 2 times / day steady, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: steady Dose: 0.2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30839402/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30839402/	Sources: https://pubmed.ncbi.nlm.nih.gov/30839402/

AEs

AE	Significance	Dose	Population
Seizure	serious, 28.6%	600 ug 1 times / day multiple, oral Highest studied dose\|Studied dose Dose: 600 ug, 1 times / day Route: oral Route: multiple Dose: 600 ug, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/results/NCT01676311?term=HUPERZINE+A&rslt=With&draw=2&rank=1 https://pubmed.ncbi.nlm.nih.gov/31638455/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://clinicaltrials.gov/ct2/show/results/NCT01676311?term=HUPERZINE+A&rslt=With&draw=2&rank=1 https://pubmed.ncbi.nlm.nih.gov/31638455/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429 CYP2A6 879 CYP2C19 2057 OATP1B1 1079 CYP1A2 2153 OATP1B3 961 CYP2E1 1060	P-gp 2052 CYP 303 MRP2 252	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTI1NTkwMSJ9fQ==	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTI1NTkwMSJ9fQ==	no [IC50 >10 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/854026#section=Biological-Test-Results Page: 75.0	no
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/27751854/	no
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/27751854/	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEyNTU5MDEifX0=	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity
CYP 303	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27751854/	no
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31132291/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31132291/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTI1NTkwMSJ9fQ==

PubMed

Title	Date	PubMed
The role of cholinergic anti-inflammatory pathway in acetic acid-induced colonic inflammation in the rat.	2013-09-05	23810507
A combination of [+] and [-]-Huperzine A improves protection against soman toxicity compared to [+]-Huperzine A in guinea pigs.	2013-03-25	23123250
Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats.	2010-10	20624417
BZYX, a novel acetylcholinesterase inhibitor, significantly improved chemicals-induced learning and memory impairments on rodents and protected PC12 cells from apoptosis induced by hydrogen peroxide.	2009-06-24	19345205
Anti-acetylcholinesterase activities of traditional Chinese medicine for treating Alzheimer's disease.	2008-09-25	18573242
Protection of red blood cell acetylcholinesterase by oral huperzine A against ex vivo soman exposure: next generation prophylaxis and sequestering of acetylcholinesterase over butyrylcholinesterase.	2008-09-25	18572153
The combination of huperzine A and imidazenil is an effective strategy to prevent diisopropyl fluorophosphate toxicity in mice.	2008-09-16	18784370
Prolonged effects of poly(lactic-co-glycolic acid) microsphere-containing huperzine A on mouse memory dysfunction induced by scopolamine.	2007-03	17309523
Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.	2006-08-29	16914529
Effects of acetylcholinesterase and butyrylcholinesterase inhibition on breathing in mice adapted or not to reduced acetylcholinesterase.	2005-01	15652380
Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease.	2005	15956816
Comparative effects of huperzine A, donepezil and rivastigmine on cortical acetylcholine level and acetylcholinesterase activity in rats.	2004-05-06	15135892
Identification of cytochrome P450 1A2 as enzyme involved in the microsomal metabolism of Huperzine A.	2003-02-14	12586202
Ginkgolide A, B, and huperzine A inhibit nitric oxide-induced neurotoxicity.	2002-10	12433056
Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine.	1998-05-22	9671090
Effect of huperzine A, a novel acetylcholinesterase inhibitor, on radial maze performance in rats.	1995-06-01	7667362

Patents

Sample Use Guides

In Vivo Use Guide

Patients in the mimopezil arm received 1 mg mimopezil daily orally during the 1-month titration period, 9 mg mimopezil as s.c. implants in the 1-month maintenance I period, and 12 mg mimopezil as s.c. implants in the 4-month maintenance II period.

Route of Administration: Other

In Vitro Use Guide

The synthetic racemic mixture (+/-)-huperzine-A was 3 times less potent than (-)-huperzine-A in vitro (IC50s of 3 x 10(-7) M and 10(-7) M, respectively) because the former consisted of a racemic mixture of the compound in which the (+)-huperzine component was considerably less potent (IC50 = 7 x 10(-6) M).

Substance Class	Chemical Created by `admin` on `Wed Apr 02 14:28:31 GMT 2025` Edited by `admin` on `Wed Apr 02 14:28:31 GMT 2025`
Record UNII	9F4GM58TAA
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HUPERZINE A MONOHYDRATE

Common Name

English

(5R,9R,11E)-5-AMINO-11-ETHYLIDENE-5,6,9,10-TETRAHYDRO-7-METHYL-5,9-METHANOCYCLOOCTA(B)PYRIDIN-2(1H)-ONE MONOHYDRATE

Preferred Name

English

5,9-Methanocycloocta[b]pyridin-2(1H)-one, 5-amino-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-, hydrate (1:1), (5R,9R,11E)-

Systematic Name

English

Code System Code Type Description

FDA UNII

9F4GM58TAA

Created by admin on Wed Apr 02 14:28:31 GMT 2025 , Edited by admin on Wed Apr 02 14:28:31 GMT 2025

PRIMARY

CAS

936244-10-9

Created by admin on Wed Apr 02 14:28:31 GMT 2025 , Edited by admin on Wed Apr 02 14:28:31 GMT 2025

PRIMARY

PUBCHEM

139070639

Created by admin on Wed Apr 02 14:28:31 GMT 2025 , Edited by admin on Wed Apr 02 14:28:31 GMT 2025

PRIMARY

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Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator