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

Molecular Formula C21H24F3N3S
Molecular Weight 407.4974
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
Drug-induced torsade de pointes.
1985 Nov-Dec
The effects of chronic treatment and withdrawal of CNS depressants on aggressive behavior.
1989 Dec
Pseudo-tetanus following trifluoperazine.
1990 Oct
Association of high prolactin levels and neuroleptics immediately postpartum.
1990 Winter
On the selection of mice for haloperidol response and non-response.
1991
Organic amnestic disorder: a long-term sequel after neuroleptic malignant syndrome.
1991 Feb 15
Pisa syndrome in an adolescent on neuroleptic medication.
1991 Mar
Folie à deux.
2005 Jul
Overview and emerging trends.
2005 Oct
Endogenous zinc in neurological diseases.
2005 Oct
Treatment of generalized anxiety disorder.
2007 Apr
Unusual case reports: Tardive oculogyric crisis (tardive syndromes).
2007 Jul
Comment on 'Topical verapamil HCL, topical trifluoroperazine, and topical magnesium sulfate for the treatment of Peyronie's disease--a placebo-controlled pilot study'.
2007 Jul
Inflammation-related genes up-regulated in schizophrenia brains.
2007 Sep 6
"Calm, but still alert": Marketing Stelazine to disturbed America, 1958-1980.
2008
Role of TRP channels and NCX in mediating hypoxia-induced [Ca(2+)](i) elevation in PC12 cells.
2008 Dec 31
Physiological hydrostatic pressure protects endothelial monolayer integrity.
2008 Jan
Preservation of protein clefts in comparative models.
2008 Jan 16
Interaction of antagonists with calmodulin: insights from molecular dynamics simulations.
2008 Jun 12
Miscellaneous.
2008 Oct
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
A molecular model for diacylglycerol acyltransferase from Mortierella ramanniana var. angulispora.
2009 Jun 28
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
The story of antipsychotics: Past and present.
2009 Oct-Dec
Molecular mechanism of trifluoperazine induces apoptosis in human A549 lung adenocarcinoma cell lines.
2009 Sep-Oct
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
Allosteric effects of the antipsychotic drug trifluoperazine on the energetics of calcium binding by calmodulin.
2010 Aug 1
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
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
Research on antidepressants in India.
2010 Jan
Research on antipsychotics in India.
2010 Jan
Anti-psychotic prescription pattern: A preliminary survey of Psychiatrists in India.
2010 Jul
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
Calcium signaling is involved in cadmium-induced neuronal apoptosis via induction of reactive oxygen species and activation of MAPK/mTOR network.
2011 Apr 22
Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle.
2011 Oct 15
Activity of trifluoperazine against replicating, non-replicating and drug resistant M. tuberculosis.
2012
Comparison of the effect of non-antifungal and antifungal agents on Candida isolates from the gastrointestinal tract.
2012 Jan
Antitubercular pharmacodynamics of phenothiazines.
2013 Apr
Avermectin induces P-glycoprotein expression in S2 cells via the calcium/calmodulin/NF-κB pathway.
2013 Apr 25
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
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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:54:33 UTC 2021
Edited
by admin
on Fri Jun 25 22:54:33 UTC 2021
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 [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
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY