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
SMILES
O[C@H]([C@@H](O)C(O)=O)C(O)=O.[H][C@]12N(C)CC[C@@]1(C)C3=C(C=CC(OC(=O)NC4=CC=CC=C4)=C3)N2C
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
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 |
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15974893 | https://www.ncbi.nlm.nih.gov/pubmed/20930279
Curator's Comment: Phenserine was licensed from the National Institute on Aging by Axonyx Corporation in 1997 for commercial development.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11708910 |
22.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
DLT: Vomiting, Nausea... Other AEs: Dizziness, Diaphoresis... Dose limiting toxicities: Vomiting (66.7%) Other AEs:Nausea (grade 3, 66.7%) Dizziness (66.7%) Sources: Page: p.487Diaphoresis (50%) Lacrimation increased (33.3%) Nausea (grade 2, 16.7%) |
10 mg single, oral MTD Dose: 10 mg Route: oral Route: single Dose: 10 mg Sources: Page: p.487 |
healthy, ADULT n = 12 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 12 Sources: Page: p.487 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Lacrimation increased | 33.3% | 20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
Diaphoresis | 50% | 20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
Dizziness | 66.7% | 20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
Vomiting | 66.7% DLT |
20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
Nausea | grade 2, 16.7% | 20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
Nausea | grade 3, 66.7% DLT |
20 mg single, oral Highest studied dose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.487 |
healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.487 |
PubMed
Title | Date | PubMed |
---|---|---|
Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action. | 2001 Nov 22 |
|
An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. | 2005 Jul |
|
Preclinical investigation of the topical administration of phenserine: transdermal flux, cholinesterase inhibition, and cognitive efficacy. | 2007 Apr |
|
Phenserine efficacy in Alzheimer's disease. | 2010 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20930279
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16049844
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
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Record UNII |
A2TJL9CO2K
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Record Status |
Validated (UNII)
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PARENT -> SALT/SOLVATE |