U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H23N3O2.C4H6O6
Molecular Weight 487.5024
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENSERINE TARTRATE

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.CN1CC[C@]2(C)[C@H]1N(C)C3=CC=C(OC(=O)NC4=CC=CC=C4)C=C23

InChI

InChIKey=XKKPTCVQEJZDGT-PWUAAHBCSA-N
InChI=1S/C20H23N3O2.C4H6O6/c1-20-11-12-22(2)18(20)23(3)17-10-9-15(13-16(17)20)25-19(24)21-14-7-5-4-6-8-14;5-1(3(7)8)2(6)4(9)10/h4-10,13,18H,11-12H2,1-3H3,(H,21,24);1-2,5-6H,(H,7,8)(H,9,10)/t18-,20+;1-,2-/m11/s1

HIDE SMILES / InChI
Molecular Formula C20H23N3O2
Molecular Weight 337.4155
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Phenserine tartrate (phenserine), a phenylcarbamate analog of physostigmine, is a long-acting and centrally active inhibitor of acetylcholinesterase (AChE). In addition to being a potent inhibitor of AChE, it has been demonstrated that phenserine inhibits the formation of beta-APP, the source of neurotoxic beta-amyloid peptide which is a major component of the extraneuronal plaques that pathologically characterize Alzheimer’s disease (AD). Phenserine was developed as a potential therapy for AD by Axonyx, under license from the National Institutes of Health/National Institute on Aging. In March 2005, Axonyx suspended patient recruitment for the ongoing Phase III trials of phenserine, after the drug failed to meet the primary endpoints of the first of these trials.

CNS Activity

Originator

National Institutes of Health
11
Curator's Comment: Phenserine was licensed from the National Institute on Aging by Axonyx Corporation in 1997 for commercial development.

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 22.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
9.87 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/16248851
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENSERINE TARTRATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
35.72 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/16248851
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENSERINE TARTRATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.53 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/16248851
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENSERINE TARTRATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
DLT: Nausea, Vomiting...
Other AEs: Dizziness, Diaphoresis...
Dose limiting toxicities:
Nausea (grade 3, 66.7%)
Vomiting (66.7%)
Other AEs:
Dizziness (66.7%)
Diaphoresis (50%)
Nausea (grade 2, 16.7%)
Lacrimation increased (33.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
10 mg single, oral
MTD
Dose: 10 mg
Route: oral
Route: single
Dose: 10 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
AEs

AEs

AESignificanceDosePopulation
Lacrimation increased 33.3%
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Diaphoresis 50%
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Dizziness 66.7%
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Vomiting 66.7%
DLT
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Nausea grade 2, 16.7%
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Nausea grade 3, 66.7%
DLT
20 mg single, oral
Highest studied dose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/16248851
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1946
 major
Sourcing

Sourcing

Vendor/AggregatorIDURL
ABI Chem
AC1OCF7V
NovoSeek
6918263
PubMed

PubMed

TitleDatePubMed
Phenserine efficacy in Alzheimer's disease.
2010
Preclinical investigation of the topical administration of phenserine: transdermal flux, cholinesterase inhibition, and cognitive efficacy.
2007-04
An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease.
2005-07
Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action.
2001-11-22
Patents

Patents

US5409948
1
US6495700
1
WO2010117727
1

Sample Use Guides

In Vivo Use Guide
A blinded titration schedule was used so that patients randomized to active treatment received 5 mg of phenserine twice daily for the first 4 weeks of the study followed by 10 mg twice daily for the next 4 weeks. Patients randomized to 15 mg of phenserine twice daily received this dose starting on week 9. Treatment at the assigned dose was continued for up to 26 weeks.
Route of Administration: Oral
In Vitro Use Guide
In vitro activity of phenserine was measured using prepared human AChE derived from plasma. The ability of the enzyme to degrade the specific substrate acetyl-(beta-methyl)thiocholine was evaluated spectrophotometrically. Phenserine inhibited AChE with IC50 of 22 nM.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:08:32 GMT 2025
Edited
by admin
on Mon Mar 31 18:08:32 GMT 2025
Record UNII
A2TJL9CO2K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
(-)-PHENSERINE (+)-TARTRATE
Preferred Name English
PHENSERINE TARTRATE
MI  
Common Name English
PYRROLO(2,3-B)INDOL-5-OL, 1,2,3,3A,8,8A-HEXAHYDRO-1,3A,8-TRIMETHYL-, PHENYLCARBAMATE (ESTER), (3AS,8AR)-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (SALT)
Common Name English
PHENSERINE TARTRATE [MI]
Common Name English
PHENSERINE (+)-TARTRATE
Common Name English
PYRROLO(2,3-B)INDOL-5-OL, 1,2,3,3A,8,8A-HEXAHYDRO-1,3A,8-TRIMETHYL-, 5-(N-PHENYLCARBAMATE), (3AS,8AR)-, (2R,3R)-2,3-DIHYDROXYBUTANEDIOATE (1:1)
Common Name English
Code System Code Type Description
PUBCHEM
6918263
Created by admin on Mon Mar 31 18:08:32 GMT 2025 , Edited by admin on Mon Mar 31 18:08:32 GMT 2025
PRIMARY
CAS
156910-61-1
Created by admin on Mon Mar 31 18:08:32 GMT 2025 , Edited by admin on Mon Mar 31 18:08:32 GMT 2025
PRIMARY
EPA CompTox
DTXSID50935570
Created by admin on Mon Mar 31 18:08:32 GMT 2025 , Edited by admin on Mon Mar 31 18:08:32 GMT 2025
PRIMARY
MERCK INDEX
m8642
Created by admin on Mon Mar 31 18:08:32 GMT 2025 , Edited by admin on Mon Mar 31 18:08:32 GMT 2025
PRIMARY Merck Index
FDA UNII
A2TJL9CO2K
Created by admin on Mon Mar 31 18:08:32 GMT 2025 , Edited by admin on Mon Mar 31 18:08:32 GMT 2025
PRIMARY
SMS_ID
300000056665
Created by admin on Mon Mar 31 18:08:32 GMT 2025 , Edited by admin on Mon Mar 31 18:08:32 GMT 2025
PRIMARY
Related Record Type Details
Structure of Tartaric Acid
PARENT -> SALT/SOLVATE
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966