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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:30:49 UTC
HMDB IDHMDB14969
Secondary Accession NumbersNone
Metabolite Identification
Common NameTrifluoperazine
DescriptionTrifluoperazine is only found in individuals that have used or taken this drug. It is a phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [PubChem]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.
Structure
Thumb
Synonyms
ValueSource
10-[3-(4-Methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)-10H-phenothiazineChEBI
10-[3-(4-METHYL-piperazin-1-yl)-propyl]-2-trifluoromethyl-10H-phenothiazineChEBI
TrifluoperazinaChEBI
TrifluoperazinumChEBI
Trifluoromethyl-10-(3'-(1-methyl-4-piperazinyl)propyl)phenothiazineChEBI
TrifluoroperazineChEBI
TrifluperazineChEBI
TrifluoperazinHMDB
TrifluoromethylperazineHMDB
TrifluroperizineHMDB
Chemical FormulaC21H24F3N3S
Average Molecular Weight407.496
Monoisotopic Molecular Weight407.164303088
IUPAC Name10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10H-phenothiazine
Traditional Nametrifluoperazine
CAS Registry Number117-89-5
SMILES
CN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(C=C3)C(F)(F)F)CC1
InChI Identifier
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
InChI KeyInChIKey=ZEWQUBUPAILYHI-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • N-alkylpiperazine
  • N-methylpiperazine
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Para-thiazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antiemetics
  • Antipsychotic Agents
  • Antipsychotics
  • Dopamine Antagonists
  • Phenothiazines
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility8.76e-03 g/LNot Available
LogP4.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0088 mg/mLALOGPS
logP4.87ALOGPS
logP4.66ChemAxon
logS-4.7ALOGPS
pKa (Strongest Basic)8.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.72 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity110.98 m3·mol-1ChemAxon
Polarizability41.94 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-03kc-9740000000-e505b8906d154e2285a4View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00831
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00831
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-2 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00831
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5365
KEGG Compound IDC07168
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTrifluoperazine
NuGOwiki LinkHMDB14969
Metagene LinkHMDB14969
METLIN IDNot Available
PubChem Compound5566
PDB IDTFP
ChEBI ID45951
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular weight:
146422.99
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. [8483075 ]
  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. [8304479 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
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.
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular weight:
60024.535
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. [19487247 ]
  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. [17620344 ]
  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. [16381668 ]
General function:
Involved in monooxygenase activity
Specific function:
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. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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. [19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
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
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [11873706 ]
  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. [8102973 ]
  4. Schmidt MH, Lee T: Investigation of striatal dopamine D2 receptor acquisition following prenatal neuroleptic exposure. Psychiatry Res. 1991 Mar;36(3):319-28. [1676523 ]
  5. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [15695070 ]
  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. [945467 ]
General function:
Involved in calcium ion binding
Specific function:
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. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis
Gene Name:
CALM1
Uniprot ID:
P62158
Molecular weight:
16837.5
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. [10592235 ]
  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. [21129983 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
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
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular weight:
51486.0
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. [17139284 ]
  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. [17016423 ]
  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. [8150214 ]
  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. [6135146 ]
General function:
Involved in dopamine receptor binding
Specific function:
Interacts with clathrin light chain A and stimulates clathrin self-assembly and clathrin-mediated endocytosis
Gene Name:
CALY
Uniprot ID:
Q9NYX4
Molecular weight:
23433.5
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [945467 ]
  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. [17407813 ]
General function:
Involved in calcium ion binding
Specific function:
Not Available
Gene Name:
S100A4
Uniprot ID:
P26447
Molecular weight:
11728.4
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. [10592235 ]
  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. [20421509 ]
General function:
Involved in calcium ion binding
Specific function:
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
Gene Name:
TNNC1
Uniprot ID:
P63316
Molecular weight:
18402.4
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. [10592235 ]
  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. [9525919 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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. [11716514 ]