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

Details

Stereochemistry ACHIRAL
Molecular Formula C22H26F3N3OS
Molecular Weight 437.522
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUPHENAZINE

SMILES

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

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 437.522
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.

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
Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride.
1970 Sep-Oct
Maintenance treatment of schizophrenia with long-acting fluphenazine.
1974 Aug
Phenothiazine-induced decompensation.
1974 Jan
The effect of 5-hydroxytrytamine synthesis inhibitors on neuroleptic-induced catalepsy in rats.
1975
Dystonic reaction to high dose propranolol.
1977 Oct 29
High vs standard dosage fluphenazine HCL in acute schizophrenia.
1978 Nov
The influence of alpha-adrenergic drugs on catalepsy induced by haloperidol or fluphenazine in rats.
1978 Sep-Oct
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
Neuroleptic-induced acute dyskinesias in rhesus monkeys.
1981
Intrauterine effect of phenothiazines.
1981 Apr 18
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
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
Drug-induced dystonia in young and elderly patients.
1988 Jul
Manic syndrome associated with zidovudine treatment.
1988 Jun 17
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
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
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
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
Case report of withdrawal syndrome after olanzapine discontinuation.
2000 Aug
Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans.
2000 Sep
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.
2003 Mar
Analysis of phenothiazine and its derivatives using LC/electrochemistry/MS and LC/electrochemistry/fluorescence.
2003 Sep 15
Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior.
2004 Feb 18
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers.
2005 Sep 1
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006 Jun
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
Neuroleptic-induced dysphagia: case report and literature review.
2007 Jan
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs.
2007 Jul 17
Chronic treatment with fluphenazine alters parameters of oxidative stress in liver and kidney of rats.
2009 Jul
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
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 23:59:29 UTC 2023
Edited
by admin
on Wed Jul 05 23:59:29 UTC 2023
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
FLUPHENAZINE ENANTHATE IMPURITY B [EP IMPURITY]
Common Name English
1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)-
Systematic Name English
NSC-62323
Code English
FLUPHENAZINE [MART.]
Common Name English
FLUPHENAZINE [MI]
Common Name English
FLUPHENAZINE ENANTATE IMPURITY B [EP IMPURITY]
Common Name English
4-(3-(2-(TRIFLUOROMETHYL)PHENOTHIAZIN-10-YL)PROPYL)-1-PIPERAZINEETHANOL
Systematic Name English
Fluphenazine [WHO-DD]
Common Name English
FLUPHENAZINE [HSDB]
Common Name English
fluphenazine [INN]
Common Name English
FLUPHENAZINE [VANDF]
Common Name English
MODITEN
Brand Name English
FLUPHENAZINE DECANOATE IMPURITY B [EP IMPURITY]
Common Name English
Classification Tree Code System Code
NDF-RT N0000007544
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
WHO-ATC N05AB02
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
WHO-VATC QN05AB02
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
NDF-RT N0000007544
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
NCI_THESAURUS C29710
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
LIVERTOX NBK548610
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
NDF-RT N0000175746
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
NDF-RT N0000007544
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 24.1
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL726
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
CAS
69-23-8
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
LACTMED
Fluphenazine
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
PUBCHEM
3372
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
RXCUI
4496
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY RxNorm
DRUG CENTRAL
1212
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
ChEMBL
CHEMBL1200951
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
FDA UNII
S79426A41Z
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
EPA CompTox
DTXSID2023068
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
DRUG BANK
DB00623
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
IUPHAR
204
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
MERCK INDEX
M5490
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY Merck Index
SMS_ID
100000080739
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
INN
946
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
NSC
62323
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
DAILYMED
S79426A41Z
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
NCI_THESAURUS
C47536
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
HSDB
3334
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
CHEBI
5123
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
EVMPD
SUB07730MIG
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-702-9
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
MESH
D005476
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
WIKIPEDIA
FLUPHENAZINE
Created by admin on Wed Jul 05 23:59:30 UTC 2023 , Edited by admin on Wed Jul 05 23:59:30 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
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