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

Details

Stereochemistry ACHIRAL
Molecular Formula C21H24F3N3S
Molecular Weight 407.4974
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIFLUOPERAZINE

SMILES

CN1CCN(CCCN2c3ccccc3Sc4ccc(cc42)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

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
Deanol in the treatment of tardive dyskinesia.
1975 Aug
Drug-induced dystonia.
1975 May
Low urinary dopamine and prediction of phenothiazine-induced Parkinsonism: a preliminary report.
1976 Jun
Drug-induced torsade de pointes.
1985 Nov-Dec
The effects of chronic treatment and withdrawal of CNS depressants on aggressive behavior.
1989 Dec
Organic amnestic disorder: a long-term sequel after neuroleptic malignant syndrome.
1991 Feb 15
Biochemical properties of a minimal functional domain with ATP-binding activity of the NTPase/helicase of hepatitis C virus.
1999 Dec
Neuroleptic malignant syndrome after venlafaxine.
2000 Jan 22
A new potent calmodulin antagonist with arylalkylamine structure: crystallographic, spectroscopic and functional studies.
2000 Mar 31
Calmodulin antagonists inhibit T-type Ca(2+) currents in mouse spermatogenic cells and the zona pellucida-induced sperm acrosome reaction.
2001 Aug 1
Voltage dependence of the [Ca2+](i) oscillations system, in the Mg2+ -stimulated oocyte of the prawn Palaemon serratus.
2001 Feb
Use of trifluoroperazine isolates a [(3)H]Ifenprodil binding site in rat brain membranes with the pharmacology of the voltage-independent ifenprodil site on N-methyl-D-aspartate receptors containing NR2B subunits.
2001 Jan
Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy.
2001 May
Calcium involvement in the luminescence control of three ophiuroid species (Echinodermata).
2002 Feb
Atypical antipsychotics: mechanism of action.
2002 Feb
Characterization of PMCA isoforms and their contribution to transcellular Ca2+ flux in MDCK cells.
2003 Jan
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
2004 Jan
Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes.
2004 Jan 9
"Wages of fear": transient threefold decrease in intracellular ATP level imposes apoptosis.
2004 Jul 23
Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4.
2004 Jun 1
Anticataleptic effect of energostim during single treatment with trifluoperazine.
2004 Mar
Search of chemical scaffolds for novel antituberculosis agents.
2005 Apr
Delirium and extrapyramidal symptoms due to a lithium-olanzapine combination therapy: a case report.
2005 Aug
Altered inducible nitric oxide synthase expression and nitric oxide production in the bladder of cats with feline interstitial cystitis.
2005 Feb
Characterization of afloqualone N-glucuronidation: species differences and identification of human UDP-glucuronosyltransferase isoform(s).
2005 Jan
Overview and emerging trends.
2005 Oct
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
Consideration of use of phenothiazines in particular trifluorperazine for epidermal growth factor receptor associated cancers.
2007
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Unusual case reports: Tardive oculogyric crisis (tardive syndromes).
2007 Jul
Activity and post antifungal effect of chlorpromazine and trifluopherazine against Aspergillus, Scedosporium and zygomycetes.
2007 Jul
Inflammation-related genes up-regulated in schizophrenia brains.
2007 Sep 6
Clozapine-induced tardive dystonia (blepharospasm).
2007 Winter
Pleiotropic effects of cadmium in mesangial cells.
2009 Aug 1
Spectroscopic and electrochemical analysis of psychotropic drugs.
2009 Jan
Finding my faith.
2009 Jan
Structure of the inhibitor W7 bound to the regulatory domain of cardiac troponin C.
2009 Jun 23
In vivo reorganization of the actin cytoskeleton in leaves of Nicotiana tabacum L. transformed with plastin-GFP. Correlation with light-activated chloroplast responses.
2009 May 29
Mechanism of catch force: tethering of thick and thin filaments by twitchin.
2010
Lithium, trifluperazine and idiopathic leucopenia: Author and reviewer perspectives on how to write a good case report.
2010 Apr
Acute akathisia with quetiapine: A case report and review of literature.
2010 Dec
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
Research on antidepressants in India.
2010 Jan
Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.
2010 Mar 3
Inhibitory effect of chlorpromazine on RANKL-induced osteoclastogenesis in mouse bone marrow cells.
2011
Comparison of the effect of non-antifungal and antifungal agents on Candida isolates from the gastrointestinal tract.
2012 Jan
Regorafenib impairs mitochondrial functions, activates AMP-activated protein kinase, induces autophagy, and causes rat hepatocyte necrosis.
2015 Jan 2
In vitro selective inhibition of human UDP-glucuronosyltransferase (UGT) 1A4 by finasteride, and prediction of in vivo drug-drug interactions.
2015 Jan 22
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.
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 [WHO-DD]
Common 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 [INN]
Common Name English
NSC-46061
Code English
Classification Tree Code System Code
NDF-RT N0000007544
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
NDF-RT N0000175746
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
NCI_THESAURUS C29710
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
WHO-VATC QN05AB06
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
NDF-RT N0000007544
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
NDF-RT N0000007544
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
NCI_THESAURUS C740
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
WHO-ATC N05AB06
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
LIVERTOX 998
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
Code System Code Type Description
HSDB
3195
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
MERCK INDEX
M11116
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00831
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
LACTMED
Trifluoperazine
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
EPA CompTox
117-89-5
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
ChEMBL
CHEMBL422
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
CAS
117-89-5
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
ECHA (EC/EINECS)
204-219-4
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
IUPHAR
214
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
MESH
D014268
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
NCI_THESAURUS
C62084
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
INN
718
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
EVMPD
SUB11288MIG
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
FDA UNII
214IZI85K3
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
PUBCHEM
5566
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
RXCUI
10800
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
TRIFLUOPERAZINE
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY
DRUG CENTRAL
2740
Created by admin on Fri Jun 25 22:54:33 UTC 2021 , Edited by admin on Fri Jun 25 22:54:33 UTC 2021
PRIMARY