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Details

Stereochemistry ACHIRAL
Molecular Formula C21H24F3N3S.2ClH
Molecular Weight 480.417
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIFLUOPERAZINE HYDROCHLORIDE

SMILES

Cl.Cl.CN1CCN(CCCN2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

InChI

InChIKey=BXDAOUXDMHXPDI-UHFFFAOYSA-N
InChI=1S/C21H24F3N3S.2ClH/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;2*1H

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

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 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

1959
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

1959
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
Trifluoroperazine for the symptomatic treatment of chorea.
1975 Mar
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
Organic amnestic disorder: a long-term sequel after neuroleptic malignant syndrome.
1991 Feb 15
Neuroleptic-induced catatonia as a stage in the progression toward neuroleptic malignant syndrome.
1992 Nov
Antitubercular activity of trifluoperazine, a calmodulin antagonist.
1992 Oct 1
Biochemical properties of a minimal functional domain with ATP-binding activity of the NTPase/helicase of hepatitis C virus.
1999 Dec
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
Cellular mechanism underlying LPS-induced inhibition of in vitro L-leucine transport across rabbit jejunum.
2002
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
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
Biotin uptake by human proximal tubular epithelial cells: cellular and molecular aspects.
2005 Apr
Delirium and extrapyramidal symptoms due to a lithium-olanzapine combination therapy: a case report.
2005 Aug
Allosteric modulation of GABA(B) receptor function in human frontal cortex.
2005 Jan
Characterization of afloqualone N-glucuronidation: species differences and identification of human UDP-glucuronosyltransferase isoform(s).
2005 Jan
Control of hepatitis C: a medicinal chemistry perspective.
2005 Jan 13
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Unusual case reports: Tardive oculogyric crisis (tardive syndromes).
2007 Jul
Physiological hydrostatic pressure protects endothelial monolayer integrity.
2008 Jan
Preservation of protein clefts in comparative models.
2008 Jan 16
Miscellaneous.
2008 Oct
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
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
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
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 Dec 15 16:13:30 GMT 2023
Edited
by admin
on Fri Dec 15 16:13:30 GMT 2023
Record UNII
6P1Y2SNF5V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIFLUOPERAZINE HYDROCHLORIDE
EP   JAN   MART.   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
10-[3-(4-Methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)phenothiazine dihydrochloride
Systematic Name English
10H-PHENOTHIAZINE, 10-(3-(4-METHYL-1-PIPERAZINYL)PROPYL)-2-(TRIFLUOROMETHYL)-, DIHYDROCHLORIDE
Common Name English
TRIFLUOPERAZINE HYDROCHLORIDE [MART.]
Common Name English
STELAZINE
Brand Name English
TRIFLUOPERAZINE DIHYDROCHLORIDE
MI  
Common Name English
TRIFLUOPERAZINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
TRIFLUOPERAZINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
TRIFLUOPERAZINE HYDROCHLORIDE [USP-RS]
Common Name English
TRIFLUOPERAZINE HCL
Common Name English
NSC-757369
Code English
TRIFLUOPERAZINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
TRIFLUOPERAZINE HYDROCHLORIDE [VANDF]
Common Name English
Trifluoperazine hydrochloride [WHO-DD]
Common Name English
TRIFLUOPERAZINE HYDROCHLORIDE [JAN]
Common Name English
TRIFLUOPERAZINE DIHYDROCHLORIDE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C740
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
NCI_THESAURUS C29710
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
Code System Code Type Description
CHEBI
9710
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
ECHA (EC/EINECS)
207-123-0
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
RS_ITEM_NUM
1685000
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
NSC
757369
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
DAILYMED
6P1Y2SNF5V
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
CAS
440-17-5
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
ChEMBL
CHEMBL422
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
PUBCHEM
66064
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
MERCK INDEX
m11116
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID1045085
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
EVMPD
SUB04956MIG
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
RXCUI
91130
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY RxNorm
NCI_THESAURUS
C904
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
DRUG BANK
DBSALT000569
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
SMS_ID
100000092799
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
FDA UNII
6P1Y2SNF5V
Created by admin on Fri Dec 15 16:13:30 GMT 2023 , Edited by admin on Fri Dec 15 16:13:30 GMT 2023
PRIMARY
Related Record Type Details
IMPURITY -> PARENT
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ACTIVE MOIETY