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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
Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE
Molecular Formula C22H26F3N3OS
Molecular Weight 437.522
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
137
Targets

Targets

Primary TargetPharmacologyConditionPotency
Substrate
656
Antagonist
2760
Inverse Agonist
79
 1.412 µM [EC50]
Antagonist
2760
Antagonist
2760
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8360
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

5.5313282E11
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
1709

inhibitor
1579
inhibitor
1752
substrate
1193

inhibitor
1837
inhibitor
1599

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1509
CYP2C19
985
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1673
 moderate [Ki 40.2 uM]
CYP2C9
1803
 weak [IC50 398.1 uM]
CYP3A4
1909
 weak [IC50 441.2 uM]
CYP2D6
1875
 yes [Ki 9.4 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
985
 yes
CYP2D6
1193
 yes
CYP3A4
1709
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1632
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
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
The therapeutic use of diazepam for akathisia.
1973 Jul-Aug
Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy.
1975 Jan-Feb
On the anticataleptic action of cyproheptadine.
1976 Aug
Schizophrenia-like reaction to diethylpropion.
1976 Nov 27
Phenothiazine-induced dystonic reaction while swimming.
1978 Oct 21
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
A case of neuroleptic malignant syndrome successfully treated with amantadine.
1982 Sep
[Malignant neuroleptics syndrome].
1984 Mar 9
Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain.
1987 Dec
[Repeated acute dystonia following administration of metoclopramide and fluphenazine].
1988 Mar 14
Affective disorder following use of phenylpropanolamine.
1990 Mar
Actions of ORG 5222 as a novel psychotropic agent.
1990 Mar
On the selection of mice for haloperidol response and non-response.
1991
Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice.
1991
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
1991 Apr 18
Incidence and correlates of acute extrapyramidal symptoms in first episode of schizophrenia.
1992
Nerve growth factor-stimulated calcium uptake into PC12 cells: uniqueness of the channel and evidence for phosphorylation.
1992 Apr
Interaction between fluoxetine and neuroleptics.
1993 May
Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex.
1993 Sep-Dec
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
1994 Mar
Effects of concomitant risperidone and lithium treatment.
1995 Jul
Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.
1995 Jul-Aug
Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.
1995 Nov-Dec
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
Case report of withdrawal syndrome after olanzapine discontinuation.
2000 Aug
Gabapentin therapy for cocaine cravings.
2000 Dec
Sexual side effects of novel antipsychotic medications.
2002 Jul 1
Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii.
2003 Aug 1
Analysis of phenothiazine and its derivatives using LC/electrochemistry/MS and LC/electrochemistry/fluorescence.
2003 Sep 15
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
2004 Apr 15
Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior.
2004 Feb 18
Olanzapine versus fluphenazine in an open trial in patients with psychotic combat-related post-traumatic stress disorder.
2004 Oct
Down-regulation of amygdala preprotachykinin A mRNA but not 3H-SP receptor binding sites in subjects affected by mood disorders and schizophrenia.
2005 Mar
Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers.
2005 Sep 1
Dopamine antagonist alters serum cortisol and prolactin secretion in lactating Holstein cows.
2006 Jun
Hybrid approach for the design of highly affine and selective dopamine D(3) receptor ligands using privileged scaffolds of biogenic amine GPCR ligands.
2007 Dec 1
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
An insight into the sialotranscriptome of the brown dog tick, Rhipicephalus sanguineus.
2010 Jul 22
Long-acting injectable antipsychotics: focus on olanzapine pamoate.
2010 Jun 24
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
147

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%).
Substance Class Chemical
Created
by admin
on Thu Jul 06 23:25:17 UTC 2023
Edited
by admin
on Thu Jul 06 23:25:17 UTC 2023
Record UNII
4MB4M45MSE
Record Status Validated (UNII)
Record Version
  • Download
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 Thu Jul 06 23:25:18 UTC 2023 , Edited by admin on Thu Jul 06 23:25:18 UTC 2023
PRIMARY
CAS
3093-66-1
Created by admin on Thu Jul 06 23:25:18 UTC 2023 , Edited by admin on Thu Jul 06 23:25:18 UTC 2023
PRIMARY
SMS_ID
100000089036
Created by admin on Thu Jul 06 23:25:18 UTC 2023 , Edited by admin on Thu Jul 06 23:25:18 UTC 2023
PRIMARY
PUBCHEM
6451517
Created by admin on Thu Jul 06 23:25:18 UTC 2023 , Edited by admin on Thu Jul 06 23:25:18 UTC 2023
PRIMARY
Related Record Type Details
Structure of FLUPHENAZINE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of FLUPHENAZINE
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