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

Details

Stereochemistry ACHIRAL
Molecular Formula C21H24F3N3S
Molecular Weight 407.496
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIFLUOPERAZINE

SMILES

CN1CCN(CCCN2C3=CC(=CC=C3SC4=C2C=CC=C4)C(F)(F)F)CC1

InChI

InChIKey=ZEWQUBUPAILYHI-UHFFFAOYSA-N
InChI=1S/C21H24F3N3S/c1-25-11-13-26(14-12-25)9-4-10-27-17-5-2-3-6-19(17)28-20-8-7-16(15-18(20)27)21(22,23)24/h2-3,5-8,15H,4,9-14H2,1H3

HIDE SMILES / InChI

Molecular Formula C21H24F3N3S
Molecular Weight 407.496
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 https://www.drugbank.ca/drugs/DB00831 | https://www.drugs.com/cdi/trifluoperazine.html | https://clinicaltrials.gov/ct2/show/NCT02600741 | http://reference.medscape.com/drug/trifluoperazine-342991

Trifluoperazine (Eskazinyl, Eskazine, Jatroneural, Modalina, Stelazine, Terfluzine, Trifluoperaz, Triftazin) is a typical antipsychotic of the phenothiazine chemical class used for the short-term treatment of certain types of anxiety. Trifluoperazine 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. The primary application of trifluoperazine is for schizophrenia. Other official indications may vary country by country, but generally, it is also indicated for use in agitation and patients with behavioral problems, severe nausea, and vomiting as well as severe anxiety. Trials have shown a moderate benefit of this drug in patients with borderline personality disorder. A 2004 meta-analysis of the studies on trifluoperazine found that it is more likely than placebo to cause extrapyramidal side effects such as akathisia, dystonia, and Parkinsonism. It is also more likely to cause somnolence and anticholinergic side effects such as red-eye and xerostomia (dry mouth).

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
STELAZINE

Approved Use

For the management of schizophrenia. Trifluoperazine HCl is effective for the short-term treatment of generalized non-psychotic anxiety. However, trifluoperazine HCl is not the first drug to be used in therapy for most patients with non-psychotic anxiety because certain risks associated with its use are not shared by common alternative treatments (i.e., benzodiazepines). When used in the treatment of non-psychotic anxiety, trifluoperazine HCl should not be administered at doses of more than 6 mg per day or for longer than 12 weeks because the use of trifluoperazine HCl at higher doses or for longer intervals may cause persistent tardive dyskinesia that may prove irreversible (see WARNINGS ). The effectiveness of trifluoperazine HCl as a treatment for non-psychotic anxiety was established in a four-week clinical multicenter study of outpatients with generalized anxiety disorder (DSM-III). This evidence does not predict that trifluoperazine HCl will be useful in patients with other non-psychotic conditions in which anxiety, or signs that mimic anxiety, are found (i.e., physical illness, organic mental conditions, agitated depression, character pathologies, etc.). Trifluoperazine HCl has not been shown effective in the management of behavioral complications in patients with mental retardation.

Launch Date

-3.38083185E11
Primary
STELAZINE

Approved Use

For the management of schizophrenia. Trifluoperazine HCl is effective for the short-term treatment of generalized non-psychotic anxiety. However, trifluoperazine HCl is not the first drug to be used in therapy for most patients with non-psychotic anxiety because certain risks associated with its use are not shared by common alternative treatments (i.e., benzodiazepines). When used in the treatment of non-psychotic anxiety, trifluoperazine HCl should not be administered at doses of more than 6 mg per day or for longer than 12 weeks because the use of trifluoperazine HCl at higher doses or for longer intervals may cause persistent tardive dyskinesia that may prove irreversible (see WARNINGS ). The effectiveness of trifluoperazine HCl as a treatment for non-psychotic anxiety was established in a four-week clinical multicenter study of outpatients with generalized anxiety disorder (DSM-III). This evidence does not predict that trifluoperazine HCl will be useful in patients with other non-psychotic conditions in which anxiety, or signs that mimic anxiety, are found (i.e., physical illness, organic mental conditions, agitated depression, character pathologies, etc.). Trifluoperazine HCl has not been shown effective in the management of behavioral complications in patients with mental retardation.

Launch Date

-3.38083185E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.053 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIFLUOPERAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10.144 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIFLUOPERAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.9 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIFLUOPERAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
yes [IC50 17.6 uM]
yes [IC50 8 uM]
yes
yes
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties.
1975
Low urinary dopamine and prediction of phenothiazine-induced Parkinsonism: a preliminary report.
1976 Jun
Extra pyramidal side effects associated with paroxetine.
1992 Dec
Antitubercular activity of trifluoperazine, a calmodulin antagonist.
1992 Oct 1
Fits and starts.
1998 Nov
In vitro susceptibility testing of Mycobacterium tuberculosis strains to trifluoperazine.
1999 Jun
Neuroleptic malignant syndrome after venlafaxine.
2000 Jan 22
Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
2000 Jul 28
Atypical antipsychotics: mechanism of action.
2002 Feb
Novel protein kinase induced during sporangial cleavage in the oomycete Phytophthora infestans.
2002 Oct
Characterization of PMCA isoforms and their contribution to transcellular Ca2+ flux in MDCK cells.
2003 Jan
Acute dystonia caused by low dosage of olanzapine.
2003 Spring
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
2004 Jan
Altered inducible nitric oxide synthase expression and nitric oxide production in the bladder of cats with feline interstitial cystitis.
2005 Feb
Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates.
2005 Nov
Steady-state kinetics and inhibitory action of antitubercular phenothiazines on mycobacterium tuberculosis type-II NADH-menaquinone oxidoreductase (NDH-2).
2006 Apr 28
Hydrogen peroxide inhibits IL-12 p40 induction in macrophages by inhibiting c-rel translocation to the nucleus through activation of calmodulin protein.
2006 Feb 15
Effect of the flavonol quercetin on ion transport in the isolated intestine of the eel, Anguilla anguilla.
2006 May
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Agricultural exposures and gastric cancer risk in Hispanic farm workers in California.
2007 Jun
Clozapine-induced tardive dystonia (blepharospasm).
2007 Winter
Physiological hydrostatic pressure protects endothelial monolayer integrity.
2008 Jan
Interaction of antagonists with calmodulin: insights from molecular dynamics simulations.
2008 Jun 12
Finding my faith.
2009 Jan
Structure of the inhibitor W7 bound to the regulatory domain of cardiac troponin C.
2009 Jun 23
The story of antipsychotics: Past and present.
2009 Oct-Dec
Mechanism of catch force: tethering of thick and thin filaments by twitchin.
2010
Allosteric effects of the antipsychotic drug trifluoperazine on the energetics of calcium binding by calmodulin.
2010 Aug 1
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
Inhibitory effect of chlorpromazine on RANKL-induced osteoclastogenesis in mouse bone marrow cells.
2011
Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle.
2011 Oct 15
Comparison of the effect of non-antifungal and antifungal agents on Candida isolates from the gastrointestinal tract.
2012 Jan
A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.
2013 Feb
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.
2013 Jun
Patents

Sample Use Guides

Initial: 2-5 mg PO q12hr Maintenance Dose: 15-20 mg/day Not to exceed 40mg/day
Route of Administration: Oral
In Vitro Use Guide
Log-phase suspension cultures of P388/S and P388/R cells were treated with ADR (Adriamycin) (0.01 to 5.0 mkg/ml) in the presence and absence of 4 mkM TFP (Trifluoperazine ) for 24 hr at 37C. Cell counts in control and treated cultures were then determined by trypan blue dye exclusion in a hemacytometer.
Substance Class Chemical
Created
by admin
on Wed Jul 05 22:40:38 UTC 2023
Edited
by admin
on Wed Jul 05 22:40:38 UTC 2023
Record UNII
214IZI85K3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIFLUOPERAZINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
PHENOTHIAZINE, 10-(3-(4-METHYL-1-PIPERAZINYL)PROPYL)-2-(TRIFLUOROMETHYL)-
Systematic Name English
TRIFLUOPERAZINE [MI]
Common Name English
TRIFLUOPERAZINE [VANDF]
Common Name English
APO-TRIFLUOPERAZINE
Brand Name English
TRIFLUOPERAZINE [HSDB]
Common Name English
FLURAZINE
Brand Name English
NSC-17474
Code English
RP-7623
Code English
10H-PHENOTHIAZINE, 10-(3-(4-METHYL-1-PIPERAZINYL)PROPYL)-2-(TRIFLUOROMETHYL)-
Systematic Name English
Trifluoperazine [WHO-DD]
Common Name English
trifluoperazine [INN]
Common Name English
NSC-46061
Code English
Classification Tree Code System Code
NDF-RT N0000007544
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
NDF-RT N0000175746
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
NCI_THESAURUS C29710
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
WHO-VATC QN05AB06
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
NDF-RT N0000007544
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
NDF-RT N0000007544
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
NCI_THESAURUS C740
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
WHO-ATC N05AB06
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
LIVERTOX NBK548927
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
Code System Code Type Description
HSDB
3195
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
MERCK INDEX
M11116
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY Merck Index
DRUG BANK
DB00831
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
LACTMED
Trifluoperazine
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
EPA CompTox
DTXSID1046928
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
ChEMBL
CHEMBL422
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
CAS
117-89-5
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
ECHA (EC/EINECS)
204-219-4
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
IUPHAR
214
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
MESH
D014268
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
NCI_THESAURUS
C62084
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
INN
718
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
EVMPD
SUB11288MIG
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
CHEBI
45951
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
FDA UNII
214IZI85K3
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
PUBCHEM
5566
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
RXCUI
10800
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY RxNorm
DAILYMED
214IZI85K3
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
NSC
17474
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
SMS_ID
100000077744
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
NSC
46061
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
WIKIPEDIA
TRIFLUOPERAZINE
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
DRUG CENTRAL
2740
Created by admin on Wed Jul 05 22:40:38 UTC 2023 , Edited by admin on Wed Jul 05 22:40:38 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY