FLUPHENAZINE MALEATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H26F3N3OS.C4H4O4
Molecular Weight	553.594
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.OCCN1CCN(CCCN2C3=CC=CC=C3SC4=CC=C(C=C24)C(F)(F)F)CC1

InChI

InChIKey=NKGQWGWZXIYMHO-BTJKTKAUSA-N

InChI=1S/C22H26F3N3OS.C4H4O4/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;5-3(6)1-2-4(7)8/h1-2,4-7,16,29H,3,8-15H2;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

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
Sources: http://www.drugbank.ca/drugs/DB00623
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Carboxylesterase 8 Target ID: CHEMBL3383 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9755905	Substrate 661
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB00623	Antagonist 2849
Serotonin 2c (5-HT2c) receptor 131 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11561066	Inverse Agonist 85	1.412 µM [EC50]
Adrenergic receptor alpha-1 171 Target ID: CHEMBL1907610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2879204	Antagonist 2849
Dopamine D1 receptor 106 Target ID: CHEMBL2056 Sources: http://www.drugbank.ca/drugs/DB00623	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 305 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/071413s019lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Analyte	Population
1.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	11.1 mg single, oral dose: 11.1 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.92 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6787637/	18.5 mg 1 times / day steady-state, oral dose: 18.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.519 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3148147/	8.57 mg single, oral dose: 8.57 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
0.52 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2313572	9.25 mg single, oral dose: 9.25 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
2.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	11.1 mg single, oral dose: 11.1 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	2.31 mg single, intravenous dose: 2.31 mg route of administration: Intravenous experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
15.3 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	11.1 mg single, oral dose: 11.1 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.62 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6787637/	18.5 mg 1 times / day steady-state, oral dose: 18.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.946 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3148147/	8.57 mg single, oral dose: 8.57 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
6.92 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2313572	9.25 mg single, oral dose: 9.25 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
11.4 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	11.1 mg single, oral dose: 11.1 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
100 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	2.31 mg single, intravenous dose: 2.31 mg route of administration: Intravenous experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
20.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	11.1 mg single, oral dose: 11.1 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6787637/	18.5 mg 1 times / day steady-state, oral dose: 18.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3148147/	8.57 mg single, oral dose: 8.57 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
13 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2313572	9.25 mg single, oral dose: 9.25 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
14.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8911886	11.1 mg single, oral dose: 11.1 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	2.31 mg single, intravenous dose: 2.31 mg route of administration: Intravenous experiment type: SINGLE co-administered:	FLUPHENAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse events
21 mg 1 times / day multiple, intramuscular 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	unhealthy, 35.4+/-10.4 Health Status: unhealthy Age Group: 35.4+/-10.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14751428	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
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	unhealthy, 44 Health Status: unhealthy Age Group: 44 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11760	Sources: https://pubmed.ncbi.nlm.nih.gov/11760
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 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

AE	Significance	Dose	Population
Akathisia	3.3% Disc. AE	21 mg 1 times / day multiple, intramuscular 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	unhealthy, 35.4+/-10.4 Health Status: unhealthy Age Group: 35.4+/-10.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14751428
Dyskinesia	3.3% Disc. AE	21 mg 1 times / day multiple, intramuscular 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	unhealthy, 35.4+/-10.4 Health Status: unhealthy Age Group: 35.4+/-10.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14751428
Hypertonia	3.3% Disc. AE	21 mg 1 times / day multiple, intramuscular 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	unhealthy, 35.4+/-10.4 Health Status: unhealthy Age Group: 35.4+/-10.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14751428
Stupor	3.3% Disc. AE	21 mg 1 times / day multiple, intramuscular 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	unhealthy, 35.4+/-10.4 Health Status: unhealthy Age Group: 35.4+/-10.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14751428
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 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 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 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=1967dc24-f2a5-4095-baa9-a9d1c5410311&type=display

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153	CYP2C19 1119

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/27/9/1078.short	moderate [Ki 40.2 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0009279704000250 Page: 5.0	weak [IC50 398.1 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0009279704000250 Page: 5.0	weak [IC50 441.2 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/27/9/1078.short	yes [Ki 9.4 uM]

Drug as victim

Target	Modality	Activity
CYP2C19 1119	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/cpb/60/12/60_c12-00719/_pdf/-char/en	yes
CYP2D6 1388	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/cpb/60/12/60_c12-00719/_pdf/-char/en	yes
CYP3A4 1946	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/cpb/60/12/60_c12-00719/_pdf/-char/en	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/23395964/ Page: 7.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5123	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5123
ChemicalBook	CB7107784	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7107784
eMolecules	732810	https://www.emolecules.com/cgi-bin/more?vid=732810
MolPort	MolPort-001-727-938	https://www.molport.com/shop/molecule-link/MolPort-001-727-938
ZINC	ZINC000019203912	http://zinc15.docking.org/substances/ZINC000019203912

PubMed

Title	Date	PubMed
Tardive dyskinesia induced by risperidone?	1996-06	8633711
Roxindole, a potential antidepressant. I. Effect on the dopamine system.	1996	8811507
Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.	1995-11-01	8868372
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.	1995-09-05	7498321
Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.	1995-07-01	8616504
Effects of concomitant risperidone and lithium treatment.	1995-07	7540798
Fluphenazine plasma levels, dosage, efficacy, and side effects.	1995-05	7726317
The natural course of pseudotumor cerebri in lithium-treated patients.	1994-08	7962691
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.	1994-03	7908055
Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients.	1994-01	8267132
Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex.	1993-09-01	7912135
Interaction between fluoxetine and neuroleptics.	1993-05	8480836
Drug-induced dystonia in young and elderly patients.	1988-07	2898212
Manic syndrome associated with zidovudine treatment.	1988-06-17	3163740
[Tardive dystonia--a case report on therapy and metaphylaxis].	1988-05	2905065
[Repeated acute dystonia following administration of metoclopramide and fluphenazine].	1988-03-14	3354100
Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain.	1987-12	2962686
A case of neuroleptic malignant syndrome in a mentally retarded adolescent.	1986-11	3804828
[Catatonia due to fluphenazine].	1986-04-01	3732946
Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes.	1984-09	6147851
[Malignant neuroleptics syndrome].	1984-03-09	6697897
Neuroleptic malignant syndrome.	1984-01-07	6146918
Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine.	1983-07	6614876
Occurrence of neuroleptic malignant syndrome in a narcoleptic patient.	1983-06	6134661
Sexual dysfunction in women using major tranquilizers.	1982-09	7146292
A case of neuroleptic malignant syndrome successfully treated with amantadine.	1982-09	7118846
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.	1982-02	6175290
Intrauterine effect of phenothiazines.	1981-04-18	7254089
Stuttering: an unusual side effect of phenothiazines.	1981-03	6110346
Fluphenazine pharmacokinetics and therapeutic response.	1981	6787637
Neuroleptic-induced acute dyskinesias in rhesus monkeys.	1981	6117919
behavior of rats and mice administered active metabolites of fluphenazine, 7-hydroxy-fluphenazine and fluphenazine-sulfoxide.	1980-11	7194019
Sleep disturbance associated with fluphenazine HCl: a case report.	1979-07	453364
Delirium associated with combined fluphenazine-clonidine therapy.	1979-05	438148
Benztropine prophylaxis of dystonic reactions.	1979-03-28	36644
Neuroleptics related to butaclamol. An investigation of the effects of chlorine substituents on the aromatic rings.	1978-12	31480
High vs standard dosage fluphenazine HCL in acute schizophrenia.	1978-11	363702
Phenothiazine-induced dystonic reaction while swimming.	1978-10-21	709286
The influence of alpha-adrenergic drugs on catalepsy induced by haloperidol or fluphenazine in rats.	1978-09-01	35783
Dystonic reaction to high dose propranolol.	1977-10-29	589060
Schizophrenia-like reaction to diethylpropion.	1976-11-27	63037
Maintenance treatment of schizophrenia with long-acting fluphenazine.	1974-08	4154028
Phenothiazine-induced decompensation.	1974-01	4587065
The therapeutic use of diazepam for akathisia.	1973-07-01	4795129
Side effects of parenteral long-acting phenothiazines.	1972-01-22	5058734
Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride.	1970-09-01	4919176
Side-effects of phenothiazines.	1967-04-01	6021008
Drug-induced extrapyramidal symptoms: their incidence and treatment.	1967-01	6016862
Dystonic reactions to phenothiazine derivatives.	1966-10	5957732
[Psuedotetanus caused by neuroleptics. Description of a case caused by fluphenazine].	1966-09-01	5991322

Patents

Sample Use Guides

In Vivo Use Guide

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 `Mon Mar 31 21:00:04 GMT 2025` Edited by `admin` on `Mon Mar 31 21:00:04 GMT 2025`
Record UNII	97151695PW
Record Status	`Validated (UNII)`
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Name

Type

Language

FLUPHENAZINE MALEATE

Common Name

English

FLUPHENAZINE MALEATE [JAN]

Preferred Name

English

2-(4-(3-(2-(TRIFLUOROMETHYL)PHENOTHIAZIN-10-YL)PROPYL)PIPERAZIN-1-YL)ETHANOL (Z)-BUT-2-ENEDIOIC ACID (1:1)

Systematic Name

English

Fluphenazine maleate [WHO-DD]

Common Name

English

FLUOROPHENAZINE MALEATE

Systematic Name

English

Code System Code Type Description

ChEMBL

CHEMBL1200951