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

Details

Stereochemistry ACHIRAL
Molecular Formula C9H13N2O5P
Molecular Weight 260.1837
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PERZINFOTEL

SMILES

OP(O)(=O)CCN1CCCNC2=C1C(=O)C2=O

InChI

InChIKey=BDABGOLMYNHHTR-UHFFFAOYSA-N
InChI=1S/C9H13N2O5P/c12-8-6-7(9(8)13)11(3-1-2-10-6)4-5-17(14,15)16/h10H,1-5H2,(H2,14,15,16)

HIDE SMILES / InChI

Molecular Formula C9H13N2O5P
Molecular Weight 260.1837
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Perzinfotel (EAA-090) is a novel squaric acid amide derivative that has been identified as a potential treatment for ischemic brain damage resulting from stroke. EAA-090 is a competitive inhibitor at the NMDA-selective subtype of the glutamate receptor. The compound demonstrates potent inhibitory activity in both in vitro and in vivo models of NMDA-induced excitotoxicity and provides neuroprotective efficacy in several animal models of stroke. EAA-090 is unique among competitive NMDA antagonists in displaying a clear separation between predicted efficacious dose and doses that induce PCP-like psychotomimetic side effects in both animals and humans. This unique profile makes EAA-090 an exciting candidate for assessing the neuroprotective potential of the competitive NMDA mechanism.

CNS Activity

Curator's Comment: A single bolus dose of Perzinfotel (EAA-090), administered intravenously following permanent occlusion of middle cerebral artery (MCA) in the rat, reduced the size of infarcted tissue by 57%

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
28.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1210 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIDOSTAURIN unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
15700 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIDOSTAURIN unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
20 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIDOSTAURIN unknown
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
MIDOSTAURIN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources:
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources:
Disc. AE: Renal insufficiency...
AEs leading to
discontinuation/dose reduction:
Renal insufficiency (grade 3-4, 2 patients)
Sources:
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
Disc. AE: Transaminases increased, Rash...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (4 patients)
Rash (3 patients)
Vomiting (3 patients)
Arrhythmia (2 patients)
Myocardial ischemia (2 patients)
Nausea (2 patients)
Sources: Page: p.75
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources: Page: p. 23
unhealthy, adult
n = 29
Health Status: unhealthy
Condition: AML
Age Group: adult
Population Size: 29
Sources: Page: p. 23
AEs

AEs

AESignificanceDosePopulation
Renal insufficiency grade 3-4, 2 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources:
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources:
Arrhythmia 2 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
Myocardial ischemia 2 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
Nausea 2 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
Rash 3 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
Vomiting 3 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
Transaminases increased 4 patients
Disc. AE
50 mg 2 times / day steady, oral
Recommended
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources: Page: p.75
unhealthy, 47 years (range: 18-60 years)
n = 345
Health Status: unhealthy
Condition: AML
Age Group: 47 years (range: 18-60 years)
Sex: M+F
Population Size: 345
Sources: Page: p.75
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 0.5 uM]
yes [IC50 0.5 uM]
yes [IC50 0.5 uM]
yes [IC50 1 uM]
yes [IC50 1 uM]
yes [IC50 1.5 uM]
yes [IC50 1.5 uM]
yes [IC50 1.7 uM]
yes [IC50 3 uM]
yes [IC50 5 uM]
yes [IC50 5 uM]
yes [IC50 5 uM]
yes [IC50 5 uM]
yes [IC50 5 uM]
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: Coadministration of ketoconazole (400 mg daily for 10 days) with a single dose of Rydapt (50 mg) on Day 6 increased AUCinf of midostaurin by 10.4-fold and CGP62221 by 3.5-fold and area under the curve over time to last measurable concentrations (AUC0-t) of CGP52421 by 1.2-fold compared to a single Rydapt dose coadministered with placebo.
Page: 7.0
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Effects of the N-methyl-D-aspartate receptor antagonist perzinfotel [EAA-090; [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid] on chemically induced thermal hypersensitivity.
2005 Jun
Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs.
2007 Dec
Functional identification of NR2 subunits contributing to NMDA receptors on substance P receptor-expressing dorsal horn neurons.
2008 Oct 10
Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.
2009 Dec
Prodrugs of perzinfotel with improved oral bioavailability.
2009 Feb 12
Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs when administered as a preanesthetic via various routes or in combination with butorphanol.
2010 Jun
Effects of perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats.
2010 Nov
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: IM and SC routes also described: http://www.ncbi.nlm.nih.gov/pubmed/20513173
30-100 mg/kg orally (rats) 10-30 mg/kg intravenous (dogs)
Route of Administration: Oral
In Vitro Use Guide
IC50 28 nM (inhibited [(3)H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid binding to NMDA receptors). IC50 477 nM (decreased the duration of spontaneous synaptic currents and inhibited NMDA-activated currents in rat hippocampal neurons).
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:31:11 UTC 2023
Edited
by admin
on Fri Dec 15 16:31:11 UTC 2023
Record UNII
FX5AUU7Z8T
Record Status Validated (UNII)
Record Version
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Name Type Language
PERZINFOTEL
INN   USAN  
INN   USAN  
Official Name English
EAA-090
Code English
perzinfotel [INN]
Common Name English
[2-(8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid
Systematic Name English
PERZINFOTEL [USAN]
Common Name English
PHOSPHONIC ACID, (2-(8,9-DIOXO-2,6-DIAZABICYCLO(5.2.0)NON-1(7)-EN-2-YL)ETHYL)-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1509
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
Code System Code Type Description
INN
8492
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
EPA CompTox
DTXSID70162846
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
USAN
PP-87
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
CAS
144912-63-0
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
PUBCHEM
6918236
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
NCI_THESAURUS
C72122
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
WIKIPEDIA
PERZINFOTEL
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
DRUG BANK
DB12365
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
FDA UNII
FX5AUU7Z8T
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
ChEMBL
CHEMBL79810
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
SMS_ID
300000034265
Created by admin on Fri Dec 15 16:31:11 UTC 2023 , Edited by admin on Fri Dec 15 16:31:11 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY