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

Details

Stereochemistry ACHIRAL
Molecular Formula C22H26F3N3OS
Molecular Weight 437.5235
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUPHENAZINE

SMILES

c1ccc2c(c1)N(CCCN3CCN(CC3)CCO)c4cc(ccc4S2)C(F)(F)F

InChI

InChIKey=PLDUPXSUYLZYBN-UHFFFAOYSA-N
InChI=1S/C22H26F3N3OS/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/h1-2,4-7,16,29H,3,8-15H2

HIDE SMILES / InChI

Molecular Formula C22H26F3N3OS
Molecular Weight 437.5235
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 parenteral long-acting phenothiazines.
1972 Jan 22
The therapeutic use of diazepam for akathisia.
1973 Jul-Aug
Maintenance treatment of schizophrenia with long-acting fluphenazine.
1974 Aug
Phenothiazine-induced decompensation.
1974 Jan
Schizophrenia-like reaction to diethylpropion.
1976 Nov 27
Dystonic reaction to high dose propranolol.
1977 Oct 29
High vs standard dosage fluphenazine HCL in acute schizophrenia.
1978 Nov
Phenothiazine-induced dystonic reaction while swimming.
1978 Oct 21
Sleep disturbance associated with fluphenazine HCl: a case report.
1979 Jul
Benztropine prophylaxis of dystonic reactions.
1979 Mar 28
Delirium associated with combined fluphenazine-clonidine therapy.
1979 May
behavior of rats and mice administered active metabolites of fluphenazine, 7-hydroxy-fluphenazine and fluphenazine-sulfoxide.
1980 Nov
Fluphenazine pharmacokinetics and therapeutic response.
1981
Intrauterine effect of phenothiazines.
1981 Apr 18
Stuttering: an unusual side effect of phenothiazines.
1981 Mar
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
[Malignant neuroleptics syndrome].
1984 Mar 9
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
A case of neuroleptic malignant syndrome in a mentally retarded adolescent.
1986 Nov
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
[Repeated acute dystonia following administration of metoclopramide and fluphenazine].
1988 Mar 14
Prolonged fever without extrapyramidal symptoms during neuroleptic treatment.
1989 Jun
Propranolol withdrawal in psychosis.
1990 Apr
Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment.
1990 Aug
Affective disorder following use of phenylpropanolamine.
1990 Mar
Actions of ORG 5222 as a novel psychotropic agent.
1990 Mar
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
Effects of concomitant risperidone and lithium treatment.
1995 Jul
Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.
1995 Jul-Aug
Fluphenazine plasma levels, dosage, efficacy, and side effects.
1995 May
Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.
1995 Nov-Dec
Roxindole, a potential antidepressant. I. Effect on the dopamine system.
1996
Tardive dyskinesia induced by risperidone?
1996 Jun
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
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
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.
2013 Jun
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 Sat Jun 26 05:45:42 UTC 2021
Edited
by admin
on Sat Jun 26 05:45:42 UTC 2021
Record UNII
S79426A41Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUPHENAZINE
HSDB   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)-
Systematic Name English
NSC-62323
Code English
FLUPHENAZINE [WHO-DD]
Common Name English
FLUPHENAZINE ENANTATE IMPURITY B [EP]
Common Name English
FLUPHENAZINE [MART.]
Common Name English
FLUPHENAZINE [MI]
Common Name English
FLUPHENAZINE ENANTHATE IMPURITY B [EP]
Common Name English
4-(3-(2-(TRIFLUOROMETHYL)PHENOTHIAZIN-10-YL)PROPYL)-1-PIPERAZINEETHANOL
Systematic Name English
FLUPHENAZINE DECANOATE IMPURITY B [EP]
Common Name English
FLUPHENAZINE [HSDB]
Common Name English
FLUPHENAZINE [INN]
Common Name English
FLUPHENAZINE [VANDF]
Common Name English
MODITEN
Brand Name English
Classification Tree Code System Code
NDF-RT N0000007544
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
WHO-ATC N05AB02
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
WHO-VATC QN05AB02
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
NDF-RT N0000007544
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
NCI_THESAURUS C29710
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
LIVERTOX 426
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
NDF-RT N0000175746
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
NDF-RT N0000007544
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 24.1
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL726
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
CAS
69-23-8
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
LACTMED
Fluphenazine
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
PUBCHEM
3372
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
RXCUI
4496
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
1212
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL1200951
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
FDA UNII
S79426A41Z
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
EPA CompTox
69-23-8
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
DRUG BANK
DB00623
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
IUPHAR
204
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
MERCK INDEX
M5490
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY Merck Index
INN
946
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
NCI_THESAURUS
C47536
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
HSDB
3334
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
EVMPD
SUB07730MIG
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-702-9
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
MESH
D005476
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
WIKIPEDIA
FLUPHENAZINE
Created by admin on Sat Jun 26 05:45:43 UTC 2021 , Edited by admin on Sat Jun 26 05:45:43 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE -> PARENT
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY