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

Details

Stereochemistry ACHIRAL
Molecular Formula C32H44F3N3O2S.2ClH
Molecular Weight 664.693
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Fluphenazine decanoate dihydrochloride

SMILES

Cl.Cl.CCCCCCCCCC(=O)OCCN1CCN(CCCN2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

InChI

InChIKey=IJIYWOFSPALWMA-UHFFFAOYSA-N
InChI=1S/C32H44F3N3O2S.2ClH/c1-2-3-4-5-6-7-8-14-31(39)40-24-23-37-21-19-36(20-22-37)17-11-18-38-27-12-9-10-13-29(27)41-30-16-15-26(25-28(30)38)32(33,34)35;;/h9-10,12-13,15-16,25H,2-8,11,14,17-24H2,1H3;2*1H

HIDE SMILES / InChI

Molecular Formula C32H44F3N3O2S
Molecular Weight 591.771
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.461
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
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
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
Benztropine prophylaxis of dystonic reactions.
1979 Mar 28
Intrauterine effect of phenothiazines.
1981 Apr 18
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
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
A case of neuroleptic malignant syndrome in a mentally retarded adolescent.
1986 Nov
Propranolol withdrawal in psychosis.
1990 Apr
Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment.
1990 Aug
Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice.
1991
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
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
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
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
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?
1999
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
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
Down-regulation of amygdala preprotachykinin A mRNA but not 3H-SP receptor binding sites in subjects affected by mood disorders and schizophrenia.
2005 Mar
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
Dopamine antagonist alters serum cortisol and prolactin secretion in lactating Holstein cows.
2006 Jun
Relapse of tardive dyskinesia due to reduction in clozapine dose.
2009 Aug
[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
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 Dec 16 19:28:53 UTC 2023
Edited
by admin
on Sat Dec 16 19:28:53 UTC 2023
Record UNII
A9G3XK83YS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Fluphenazine decanoate dihydrochloride
Common Name English
Decanoic acid, 2-[4-[3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl]-1-piperazinyl]ethyl ester, hydrochloride (1:2)
Systematic Name English
2-[4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazinyl]ethyl decanoate dihydrochloride
Systematic Name English
Code System Code Type Description
CAS
2376-65-0
Created by admin on Sat Dec 16 19:28:54 UTC 2023 , Edited by admin on Sat Dec 16 19:28:54 UTC 2023
PRIMARY
RS_ITEM_NUM
1280803
Created by admin on Sat Dec 16 19:28:54 UTC 2023 , Edited by admin on Sat Dec 16 19:28:54 UTC 2023
PRIMARY
PUBCHEM
24745024
Created by admin on Sat Dec 16 19:28:54 UTC 2023 , Edited by admin on Sat Dec 16 19:28:54 UTC 2023
PRIMARY
FDA UNII
A9G3XK83YS
Created by admin on Sat Dec 16 19:28:54 UTC 2023 , Edited by admin on Sat Dec 16 19:28:54 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE