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Details

Stereochemistry ACHIRAL
Molecular Formula C22H26F3N3OS.2C4H4O4
Molecular Weight 669.666
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of FLUPHENAZINE DIMALEATE

SMILES

OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OCCN1CCN(CCCN2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

InChI

InChIKey=GTJLCONXCUYJOF-SPIKMXEPSA-N
InChI=1S/C22H26F3N3OS.2C4H4O4/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29;2*5-3(6)1-2-4(7)8/h1-2,4-7,16,29H,3,8-15H2;2*1-2H,(H,5,6)(H,7,8)/b;2*2-1-

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including

Fluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation. Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

CNS Activity

Originator

Squibb von Heyden
7
Curator's Comment: Introduced in 1959

Approval Year

1959
138
Targets

Targets

Primary TargetPharmacologyConditionPotency
Substrate
661
Antagonist
2778
Inverse Agonist
80
 1.412 µM [EC50]
Antagonist
2778
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
FLUPHENAZINE DECANOATE

Approved Use

Fluphenazine Decanoate Injection is a long­acting parenteral antipsychotic drug intended for use in the management of patients requiring prolonged parenteral neuroleptic therapy (e.g., chronic schizophrenics).

Launch Date

1987
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.3 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8911886
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
261 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8911886
2.5 mg 3 times / 3 days multiple, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.52 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/2313572
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6.92 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/2313572
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.4 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8911886
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12.3 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8911886
2.5 mg 3 times / 3 days multiple, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/2313572
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.6%
EXPERIMENT
https://www.agilent.com/cs/library/applications/5991-2497EN.pdf
FLUPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
Disc. AE: Akathisia, Dyskinesia...
AEs leading to
discontinuation/dose reduction:
Akathisia (3.3%)
Dyskinesia (3.3%)
Hypertonia (3.3%)
Stupor (3.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
250 mg 1 times / week multiple, intramuscular
Highest studied dose
Dose: 250 mg, 1 times / week
Route: intramuscular
Route: multiple
Dose: 250 mg, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11760
Page: p.1438
unhealthy, 44
n = 25
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 44
Sex: M+F
Population Size: 25
Sources:
https://pubmed.ncbi.nlm.nih.gov/11760
Page: p.1438
Sources:
https://pubmed.ncbi.nlm.nih.gov/11760
Page: p.1438
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
unhealthy
Health Status: unhealthy
Condition: Schizophrenia
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
Disc. AE: Tardive dyskinesia, Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Tardive dyskinesia
Neuroleptic malignant syndrome
Fall
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
AEs

AEs

AESignificanceDosePopulation
Akathisia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
Dyskinesia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
Hypertonia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
Stupor 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/14751428
Page: p.315
Fall Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
unhealthy
Health Status: unhealthy
Condition: Schizophrenia
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
Neuroleptic malignant syndrome Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
unhealthy
Health Status: unhealthy
Condition: Schizophrenia
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
Tardive dyskinesia Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
unhealthy
Health Status: unhealthy
Condition: Schizophrenia
Sources:
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
inhibitor
1767
substrate
1217

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524
CYP2C19
991
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 moderate [Ki 40.2 uM]
CYP2C9
1819
 weak [IC50 398.1 uM]
CYP3A4
1925
 weak [IC50 441.2 uM]
CYP2D6
1891
 yes [Ki 9.4 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
991
 yes
CYP2D6
1217
 yes
CYP3A4
1737
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:5123
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5123
ChemicalBook
CB7107784
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7107784
MolPort
MolPort-001-727-938
https://www.molport.com/shop/molecule-link/MolPort-001-727-938
ZINC
ZINC000019203912
http://zinc15.docking.org/substances/ZINC000019203912
eMolecules
732810
https://www.emolecules.com/cgi-bin/more?vid=732810
PubMed

PubMed

TitleDatePubMed
[Psuedotetanus caused by neuroleptics. Description of a case caused by fluphenazine].
1966 Sep-Oct
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy.
1975 Jan-Feb
Schizophrenia-like reaction to diethylpropion.
1976 Nov 27
Dystonic reaction to high dose propranolol.
1977 Oct 29
Sleep disturbance associated with fluphenazine HCl: a case report.
1979 Jul
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
Occurrence of neuroleptic malignant syndrome in a narcoleptic patient.
1983 Jun
[Catatonia due to fluphenazine].
1986 Apr 1
A case of neuroleptic malignant syndrome in a mentally retarded adolescent.
1986 Nov
Drug-induced dystonia in young and elderly patients.
1988 Jul
Actions of ORG 5222 as a novel psychotropic agent.
1990 Mar
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
1994 Mar
Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.
1995 Nov-Dec
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.
1995 Sep 5
Roxindole, a potential antidepressant. I. Effect on the dopamine system.
1996
Tardive dyskinesia induced by risperidone?
1996 Jun
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?
1999
Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats.
1999 Aug 20
Sexual side effects of novel antipsychotic medications.
2002 Jul 1
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
2004 Apr 15
Invited review: fluphenazine augments retinal oxidative stress.
2005 Aug
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Incorporating clinical guidelines through clinician decision-making.
2008 Feb 29
Relapse of tardive dyskinesia due to reduction in clozapine dose.
2009 Aug
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Patents

JP2007525670A
148

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Fluphenazine Decanoate Injection may be given IM or SC
For most patients, a dose of 12.5 to 25 mg (0.5 to 1 mL) may be given to initiate therapy.
Route of Administration: Intramuscular
In Vitro Use Guide
30uM Fluphenazine inhibited the high-threshold Ca2 channel current in rat sympathetic neurons (blocking by 66%).
Name Type Language
FLUPHENAZINE DIMALEATE
Common Name English
1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)PHENOTHIAZIN-10-YL)PROPYL)-, MALEATE (1:2)
Systematic Name English
1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)-, (2Z)-2-BUTENEDIOATE (1:2) (SALT)
Systematic Name English
Code System Code Type Description
FDA UNII
4MB4M45MSE
Created by admin on Sat Dec 16 18:07:35 GMT 2023 , Edited by admin on Sat Dec 16 18:07:35 GMT 2023
PRIMARY
CAS
3093-66-1
Created by admin on Sat Dec 16 18:07:35 GMT 2023 , Edited by admin on Sat Dec 16 18:07:35 GMT 2023
PRIMARY
SMS_ID
100000089036
Created by admin on Sat Dec 16 18:07:35 GMT 2023 , Edited by admin on Sat Dec 16 18:07:35 GMT 2023
PRIMARY
PUBCHEM
6451517
Created by admin on Sat Dec 16 18:07:35 GMT 2023 , Edited by admin on Sat Dec 16 18:07:35 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of FLUPHENAZINE
NIH
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