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Identification
Name Trifluoperazine
Accession Number DB00831 (APRD00173, DB08616)
Type small molecule
Groups approved
Description

A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Trifluoperazin
  • Trifluoperazina
  • Trifluoperazine Dihydrochloride
  • Trifluoperazine HCl
  • Trifluoperazine Hydrochloride
  • Trifluoromethylperazine
  • Trifluoroperazine
  • Trifluoroperazine Dihydrochloride
  • Trifluoroperazine Hydrochloride
  • Trifluperazine
  • Trifluroperizine
  • Triphthazine Dihydrochloride
  • Tryptazine Dihydrochloride
Brand names
  • Eskazine
  • Eskazinyl
  • Fluoperazine
  • Jatroneural
  • Modalina
  • Novo-Trifluzine
  • Stelazine
  • Stellazine
  • Synklor
  • Terfluzine
  • Trazine
  • Triflurin
  • Triftazin
  • Triftazine
  • Triperazine
  • Triphtazin
  • Triphtazine
  • Triphthasine
  • Triphthazine
  • Tryptazine
Brand name mixtures
  • Parmodalin (Tranylcypromine + Trifluoperazine)
  • Stelabid Forte (Isopropamide Iodide + Trifluoperazine Hydrochloride)
  • Stelabid No 1 (Isopropamide Iodide + Trifluoperazine Hydrochloride)
  • Stelabid No 2 (Isopropamide Iodide + Trifluoperazine Hydrochloride)
Categories
  • Antiemetics
  • Antipsychotics
  • Dopamine Antagonists
  • Phenothiazines
  • Antipsychotic Agents
CAS number 117-89-5
Weight Average: 407.496
Monoisotopic: 407.164303088
Chemical Formula C21H24F3N3S
InChI Key InChIKey=ZEWQUBUPAILYHI-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10H-phenothiazine
SMILES
CN1CCN(CCCN2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1
Plain Text
Mass Spec show (10.1 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenothiazines
Substructures
  • Ethers
  • Phenothiazines
  • Aliphatic and Aryl Amines
  • Piperazines
  • Thiazines
  • Halogen Derivatives
  • Benzene and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
Pharmacology
Indication For the treatment of anxiety disorders, depressive symptoms secondary to anxiety and agitation.
Pharmacodynamics Trifluoperazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Trifluoperazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.
Mechanism of action 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life 10-20 hours
Clearance Not Available
Toxicity Symptoms of overdose include agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, and restlessness.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
  • Sandoz inc
  • Wockhardt eu operations (swiss) ag
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Ivax pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Syrup Oral
Tablet Oral
Prices
Unit description Cost Unit
Trifluoperazine HCl 10 mg tablet 1.7 USD tablet
Trifluoperazine 10 mg tablet 1.63 USD tablet
Trifluoperazine HCl 5 mg tablet 1.09 USD tablet
Trifluoperazine 5 mg tablet 1.08 USD tablet
Trifluoperazine HCl 2 mg tablet 0.89 USD tablet
Trifluoperazine 2 mg tablet 0.86 USD tablet
Trifluoperazine HCl 1 mg tablet 0.59 USD tablet
Trifluoperazine 1 mg tablet 0.58 USD tablet
Apo-Trifluoperazine 20 mg Tablet 0.58 USD tablet
Apo-Trifluoperazine 10 mg Tablet 0.29 USD tablet
Apo-Trifluoperazine 5 mg Tablet 0.24 USD tablet
Apo-Trifluoperazine 2 mg Tablet 0.18 USD tablet
Apo-Trifluoperazine 1 mg Tablet 0.14 USD tablet
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 0.0122 mg/mL at 24 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP 4.9 PhysProp
logS -4.52 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 8.76e-03 g/l ALOGPS
logP 4.87 ALOGPS
logP 4.66 ChemAxon Molconvert
logS -4.67 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 9.72 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 110.98 ChemAxon Molconvert
polarizability 41.94 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07168 Link_out
PubChem Compound 5566 Link_out
PubChem Substance 46507961 Link_out
ChemSpider 5365 Link_out
BindingDB 50001886 Link_out
ChEBI 45951 Link_out
ChEMBL 45951 Link_out
Therapeutic Targets Database DAP000034 Link_out
PharmGKB PA451771 Link_out
HET TFP Link_out
Drug Product Database 776505 Link_out
RxList http://www.rxlist.com/cgi/generic3/trifluo.htm Link_out
Drugs.com http://www.drugs.com/cdi/trifluoperazine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tri1412.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Trifluoperazine Link_out
ATC Codes
  • N05AB06
AHFS Codes
  • 28:16.08.24
PDB Entries Not Available
FDA label Not Available
MSDS show (73.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
  3. Lahti RA, Evans DL, Stratman NC, Figur LM: Dopamine D4 versus D2 receptor selectivity of dopamine receptor antagonists: possible therapeutic implications. Eur J Pharmacol. 1993 Jun 4;236(3):483-6. Pubmed
  4. Schmidt MH, Lee T: Investigation of striatal dopamine D2 receptor acquisition following prenatal neuroleptic exposure. Psychiatry Res. 1991 Mar;36(3):319-28. Pubmed
  5. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. Pubmed
  6. Seeman P, Lee T, Chau-Wong M, Wong K: Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature. 1976 Jun 24;261(5562):717-9. Pubmed

2. D1 dopamine receptor-interacting protein calcyon

Pharmacological action: yes
Actions: antagonist

May have a role in potentiating calcium ion-dependent signaling

Organism class: human
UniProt ID: Q9NYX4 Link_out
Gene: DRD1IP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Seeman P, Lee T, Chau-Wong M, Wong K: Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature. 1976 Jun 24;261(5562):717-9. Pubmed
  3. Madrid PB, Polgar WE, Toll L, Tanga MJ: Synthesis and antitubercular activity of phenothiazines with reduced binding to dopamine and serotonin receptors. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3014-7. Epub 2007 Mar 24. Pubmed

3. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Fujinaga M, Hoffman BB, Baden JM: Receptor subtype and intracellular signal transduction pathway associated with situs inversus induced by alpha 1 adrenergic stimulation in rat embryos. Dev Biol. 1994 Apr;162(2):558-67. Pubmed
  4. Huerta-Bahena J, Villalobos-Molina R, Garcia-Sainz JA: Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects. Mol Pharmacol. 1983 Jan;23(1):67-70. Pubmed

4. Calmodulin

Pharmacological action: unknown
Actions: inhibitor

Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases

Organism class: human
UniProt ID: P62158 Link_out
Gene: CALM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  2. Torres-Piedra M, Figueroa M, Hernandez-Abreu O, Ibarra-Barajas M, Navarrete-Vazquez G, Estrada-Soto S: Vasorelaxant effect of flavonoids through calmodulin inhibition: Ex vivo, in vitro, and in silico approaches. Bioorg Med Chem. 2011 Jan 1;19(1):542-6. Epub 2010 Nov 4. Pubmed

5. Troponin C, slow skeletal and cardiac muscles

Pharmacological action: unknown

Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments

Organism class: human
UniProt ID: P63316 Link_out
Gene: TNNC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  2. Kleerekoper Q, Liu W, Choi D, Putkey JA: Identification of binding sites for bepridil and trifluoperazine on cardiac troponin C. J Biol Chem. 1998 Apr 3;273(14):8153-60. Pubmed

6. Protein S100-A4

Pharmacological action: unknown
Actions: inhibitor
Organism class: human
UniProt ID: P26447 Link_out
Gene: S100A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  2. Malashkevich VN, Dulyaninova NG, Ramagopal UA, Liriano MA, Varney KM, Knight D, Brenowitz M, Weber DJ, Almo SC, Bresnick AR: Phenothiazines inhibit S100A4 function by inducing protein oligomerization. Proc Natl Acad Sci U S A. 2010 May 11;107(19):8605-10. Epub 2010 Apr 26. Pubmed
Enzymes

1. Xanthine dehydrogenase/oxidase

Actions: conversion inhibitor

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups

UniProt ID: P47989 Link_out
Gene: XDH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hirata Y, Ishii K, Taguchi T, Suita S, Takeshige K: Conversion of xanthine dehydrogenase to xanthine oxidase during ischemia of the rat small intestine and the effect of trifluoperazine on the conversion. J Pediatr Surg. 1993 Apr;28(4):597-600. Pubmed
  2. Greene EL, Paller MS: Calcium and free radicals in hypoxia/reoxygenation injury of renal epithelial cells. Am J Physiol. 1994 Jan;266(1 Pt 2):F13-20. Pubmed

2. UDP-glucuronosyltransferase 1-4

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22310 Link_out
Gene: UGT1A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kerdpin O, Mackenzie PI, Bowalgaha K, Finel M, Miners JO: Influence of N-terminal domain histidine and proline residues on the substrate selectivities of human UDP-glucuronosyltransferase 1A1, 1A6, 1A9, 2B7, and 2B10. Drug Metab Dispos. 2009 Sep;37(9):1948-55. Epub 2009 Jun 1. Pubmed
  2. Fujiwara R, Nakajima M, Yamanaka H, Katoh M, Yokoi T: Interactions between human UGT1A1, UGT1A4, and UGT1A6 affect their enzymatic activities. Drug Metab Dispos. 2007 Oct;35(10):1781-7. Epub 2007 Jul 9. Pubmed
  3. Uchaipichat V, Mackenzie PI, Elliot DJ, Miners JO: Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) “probes” for human udp-glucuronosyltransferases. Drug Metab Dispos. 2006 Mar;34(3):449-56. Epub 2005 Dec 28. Pubmed

3. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on August 12, 2011 08:30

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.