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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.

CNS Activity

Originator

Squibb von Heyden
7
Curator's Comment: Introduced in 1959

Approval Year

1959
138
Targets

Targets

Primary TargetPharmacologyConditionPotency
Substrate
661
Antagonist
2778
Inverse Agonist
80
 1.412 µM [EC50]
Antagonist
2778
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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

1987
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
1737

inhibitor
1587
inhibitor
1767
substrate
1217

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524
CYP2C19
991
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 moderate [Ki 40.2 uM]
CYP2C9
1819
 weak [IC50 398.1 uM]
CYP3A4
1925
 weak [IC50 441.2 uM]
CYP2D6
1891
 yes [Ki 9.4 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
991
 yes
CYP2D6
1217
 yes
CYP3A4
1737
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
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
Dystonic reactions to phenothiazine derivatives.
1966 Oct
[Psuedotetanus caused by neuroleptics. Description of a case caused by fluphenazine].
1966 Sep-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
Maintenance treatment of schizophrenia with long-acting fluphenazine.
1974 Aug
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
High vs standard dosage fluphenazine HCL in acute schizophrenia.
1978 Nov
Phenothiazine-induced dystonic reaction while swimming.
1978 Oct 21
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
Neuroleptic-induced acute dyskinesias in rhesus monkeys.
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
Manic syndrome associated with zidovudine treatment.
1988 Jun 17
[Repeated acute dystonia following administration of metoclopramide and fluphenazine].
1988 Mar 14
[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
Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment.
1990 Aug
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
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.
1995 Sep 5
Roxindole, a potential antidepressant. I. Effect on the dopamine system.
1996
Tardive dyskinesia induced by risperidone?
1996 Jun
Patents

Patents

JP2007525670A
148

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 GMT 2023
Edited
by admin
on Sat Dec 16 19:28:53 GMT 2023
Record UNII
A9G3XK83YS
Record Status Validated (UNII)
Record Version
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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 GMT 2023 , Edited by admin on Sat Dec 16 19:28:54 GMT 2023
PRIMARY
RS_ITEM_NUM
1280803
Created by admin on Sat Dec 16 19:28:54 GMT 2023 , Edited by admin on Sat Dec 16 19:28:54 GMT 2023
PRIMARY
PUBCHEM
24745024
Created by admin on Sat Dec 16 19:28:54 GMT 2023 , Edited by admin on Sat Dec 16 19:28:54 GMT 2023
PRIMARY
FDA UNII
A9G3XK83YS
Created by admin on Sat Dec 16 19:28:54 GMT 2023 , Edited by admin on Sat Dec 16 19:28:54 GMT 2023
PRIMARY
Related Record Type Details
Structure of FLUPHENAZINE DECANOATE
PARENT -> SALT/SOLVATE
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