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

Details

Stereochemistry ACHIRAL
Molecular Formula C29H38F3N3O2S
Molecular Weight 549.691
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUPHENAZINE ENANTHATE

SMILES

CCCCCCC(=O)OCCN1CCN(CCCN2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

InChI

InChIKey=LRWSFOSWNAQHHW-UHFFFAOYSA-N
InChI=1S/C29H38F3N3O2S/c1-2-3-4-5-11-28(36)37-21-20-34-18-16-33(17-19-34)14-8-15-35-24-9-6-7-10-26(24)38-27-13-12-23(22-25(27)35)29(30,31)32/h6-7,9-10,12-13,22H,2-5,8,11,14-21H2,1H3

HIDE SMILES / InChI

Molecular Formula C29H38F3N3O2S
Molecular Weight 549.691
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.

Originator

Curator's Comment: Introduced in 1959

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
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
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
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
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
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
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
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%
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: 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: 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: 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: Page: p.1438
unhealthy, 44
n = 25
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 44
Sex: M+F
Population Size: 25
Sources: Page: p.1438
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Disc. AE: Tardive dyskinesia, Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Tardive dyskinesia
Neuroleptic malignant syndrome
Fall
Sources:
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: 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: 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: 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: 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: 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: 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: 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: Page: p.315
Fall Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Tardive dyskinesia Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Dystonic reactions to phenothiazine derivatives.
1966 Oct
Side-effects of phenothiazines.
1967 Apr 1
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride.
1970 Sep-Oct
Side effects of parenteral long-acting phenothiazines.
1972 Jan 22
The therapeutic use of diazepam for akathisia.
1973 Jul-Aug
Phenothiazine-induced decompensation.
1974 Jan
Schizophrenia-like reaction to diethylpropion.
1976 Nov 27
Dystonic reaction to high dose propranolol.
1977 Oct 29
Neuroleptics related to butaclamol. An investigation of the effects of chlorine substituents on the aromatic rings.
1978 Dec
Delirium associated with combined fluphenazine-clonidine therapy.
1979 May
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
Sexual dysfunction in women using major tranquilizers.
1982 Sep
A case of neuroleptic malignant syndrome successfully treated with amantadine.
1982 Sep
Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine.
1983 Jul
Occurrence of neuroleptic malignant syndrome in a narcoleptic patient.
1983 Jun
Neuroleptic malignant syndrome.
1984 Jan 7
Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes.
1984 Sep
[Catatonia due to fluphenazine].
1986 Apr 1
Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain.
1987 Dec
Drug-induced dystonia in young and elderly patients.
1988 Jul
Manic syndrome associated with zidovudine treatment.
1988 Jun 17
[Tardive dystonia--a case report on therapy and metaphylaxis].
1988 May
Prolonged fever without extrapyramidal symptoms during neuroleptic treatment.
1989 Jun
Behavioral and electroencephalographic effects of a depot type neuroleptic fluphenazine decanoate, in rats.
1989 Nov
Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease.
1990
Propranolol withdrawal in psychosis.
1990 Apr
Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment.
1990 Aug
Actions of ORG 5222 as a novel psychotropic agent.
1990 Mar
Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.
1991
On the selection of mice for haloperidol response and non-response.
1991
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
1991 Apr 18
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
The natural course of pseudotumor cerebri in lithium-treated patients.
1994 Aug
Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients.
1994 Jan
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
1994 Mar
Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.
1995 Jul-Aug
Roxindole, a potential antidepressant. I. Effect on the dopamine system.
1996
Tardive dyskinesia induced by risperidone?
1996 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
Incorporating clinical guidelines through clinician decision-making.
2008 Feb 29
Relapse of tardive dyskinesia due to reduction in clozapine dose.
2009 Aug
Effects of omega-3 essential fatty acids (omega-3 EFAs) on motor disorders and memory dysfunction typical neuroleptic-induced: behavioral and biochemical parameter.
2010 Apr
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
An insight into the sialotranscriptome of the brown dog tick, Rhipicephalus sanguineus.
2010 Jul 22
[A case of drug-induced syndrome of inappropriate secretion of antidiuretic hormone].
2010 Jul-Aug
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
Antitubercular pharmacodynamics of phenothiazines.
2013 Apr
Patents

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 Wed Jul 05 22:45:38 UTC 2023
Edited
by admin
on Wed Jul 05 22:45:38 UTC 2023
Record UNII
QSB34YF0W9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUPHENAZINE ENANTHATE
MI   ORANGE BOOK   USP   VANDF  
Common Name English
FLUPHENAZINE ENANTATE [MART.]
Common Name English
FLUPHENAZINI ENANTAS [WHO-IP LATIN]
Common Name English
FLUPHENAZINE ENANTHATE [USP MONOGRAPH]
Common Name English
FLUPHENAZINE ENANTATE [EP MONOGRAPH]
Common Name English
SQ 16,114
Code English
2-(4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)PIPERAZIN-1-YL)ETHYL HEPTANOATE
Systematic Name English
FLUFENAN
Common Name English
FLUPHENAZINE ENANTHATE [JAN]
Common Name English
PROLIXIN ENANTHATE
Common Name English
FLUPHENAZINE ENANTHATE [MI]
Common Name English
FLUPHENAZINE DECANOATE IMPURITY C [EP IMPURITY]
Common Name English
FLUPHENAZINE ENANTHATE [VANDF]
Common Name English
Fluphenazine enantate [WHO-DD]
Common Name English
FLUPHENAZINE ENANTATE [WHO-IP]
Common Name English
SQ 16144
Code English
FLUPHENAZINE ENANTHATE [ORANGE BOOK]
Common Name English
HEPTANOIC ACID, 2-(4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)-1-PIPERAZINYL)ETHYL ESTER
Common Name English
FLUPHENAZINE ENANTATE
EP   MART.   WHO-DD   WHO-IP  
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29710
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
Code System Code Type Description
DRUG CENTRAL
1214
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
CAS
2746-81-8
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
FLUPHENAZINE ENANTHATE
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY Description: A pale yellow, viscous liquid or a yellow, crystalline, oily solid; odour, faint, ester-like. Miscibility: Immiscible with water; miscible with dehydrated ethanol R and ether R. Category: Neuroleptic. Storage: Fluphenazine enantate should be kept in a well-closed container, protected from light. Definition: Fluphenazine enantate contains not less than 98.5% and not more than 101.5% of C29H38F3N3O2S, calculated with reference to the dried substance.
NCI_THESAURUS
C65726
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
ECHA (EC/EINECS)
220-385-0
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
RXCUI
30129
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY RxNorm
EVMPD
SUB02231MIG
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
FDA UNII
QSB34YF0W9
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
PUBCHEM
3389
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
MESH
C017610
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
DRUG BANK
DBSALT000777
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
SMS_ID
100000087130
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
MERCK INDEX
M5490
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY Merck Index
ChEMBL
CHEMBL1200951
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
EPA CompTox
DTXSID6023070
Created by admin on Wed Jul 05 22:45:38 UTC 2023 , Edited by admin on Wed Jul 05 22:45:38 UTC 2023
PRIMARY
Related Record Type Details
IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY