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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2018-05-20 20:13:29 UTC
HMDB IDHMDB0015013
Secondary Accession Numbers
  • HMDB15013
Metabolite Identification
Common NameFlupenthixol
DescriptionFlupentixol is an antipsychotic neuroleptic drug. It is a thioxanthene, and therefore closely related to the phenothiazines. Its primary use is as a long acting injection given two or three weekly to people with schizophrenia who have a poor compliance with medication and suffer frequent relapses of illness. It is a D1 and D2 receptor antagonist.
Structure
Thumb
Synonyms
ValueSource
2-Trifluoromethyl-9-(3-(4-(2-hydroxyethyl)piperazin-1-yl)propylidene)thioxantheneChEBI
2-Trifluoromethyl-9-(3-(4-(beta-hydroxyethyl)-1-piperazinyl)propylidene)thioxantheneChEBI
4-(3-(2-(Trifluoromethyl)-9H-thioxanthen-9-ylidene)propyl)-1-piperazineethanolChEBI
4-(3-(2-(Trifluoromethyl)thioxanthen-9-ylidene)propyl)-1-piperazineethanolChEBI
FlupentixolChEBI
FlupentixolumChEBI
2-Trifluoromethyl-9-(3-(4-(b-hydroxyethyl)-1-piperazinyl)propylidene)thioxantheneGenerator
2-Trifluoromethyl-9-(3-(4-(β-hydroxyethyl)-1-piperazinyl)propylidene)thioxantheneGenerator
FlupenthixoleHMDB
Chemical FormulaC23H27F3N2OS
Average Molecular Weight436.533
Monoisotopic Molecular Weight436.179618801
IUPAC Name2-(4-{3-[2-(trifluoromethyl)-9,9a-dihydro-4aH-thioxanthen-9-ylidene]propyl}piperazin-1-yl)ethan-1-ol
Traditional Nameflupenthixol
CAS Registry Number2709-56-0
SMILES
[H]C(CCN1CCN(CCO)CC1)=C1C2C=C(C=CC2SC2=C1C=CC=C2)C(F)(F)F
InChI Identifier
InChI=1S/C23H27F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,20,22,29H,3,9-15H2
InChI KeyDTTVNHWDONBIKE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thioxanthenes. These are organic polycyclic compounds containing a thioxanthene moiety, which is an aromatic tricycle derived from xanthene by replacing the oxygen atom with a sulfur atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiopyrans
Sub Class1-benzothiopyrans
Direct ParentThioxanthenes
Alternative Parents
Substituents
  • Thioxanthene
  • Thiochromane
  • Aryl thioether
  • N-alkylpiperazine
  • Alkylarylthioether
  • 1,4-diazinane
  • Piperazine
  • Thiopyran
  • Benzenoid
  • Tertiary aliphatic amine
  • 1,2-aminoalcohol
  • Tertiary amine
  • Azacycle
  • Alkanolamine
  • Thioether
  • Organic oxygen compound
  • Primary alcohol
  • Alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organic nitrogen compound
  • Amine
  • Alkyl halide
  • Organopnictogen compound
  • Alkyl fluoride
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.003 g/LNot Available
LogP4.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.003 g/LALOGPS
logP4.12ALOGPS
logP3.54ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)15.59ChemAxon
pKa (Strongest Basic)8.51ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.71 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity120.93 m³·mol⁻¹ChemAxon
Polarizability45.28 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-052f-9676500000-6b1399e0dd965860c60cView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0kfx-7343900000-bb450af2259a54640db1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0201900000-095389998f2b63d484e5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0aor-1914300000-8295bd965255669954f6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-015i-4901000000-783ed0fccbbc28c48ceeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0000900000-9ce18246bedc83edf347View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-1401900000-aee927a7c2a7b4e811f1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9201000000-b5c6ccae989978ac9b0eView in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00875 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00875 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00875
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFlupentixol
METLIN IDNot Available
PubChem Compound25137855
PDB IDNot Available
ChEBI ID5121
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in carboxy-lyase activity
Specific function:
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name:
DDC
Uniprot ID:
P20711
Molecular weight:
53893.755
References
  1. Zhu MY, Juorio AV, Paterson IA, Boulton AA: Regulation of aromatic L-amino acid decarboxylase in rat striatal synaptosomes: effects of dopamine receptor agonists and antagonists. Br J Pharmacol. 1994 May;112(1):23-30. [PubMed:7913379 ]
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. [PubMed:11752352 ]
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706 ]
  3. Ogren SO, Hall H, Kohler C, Magnusson O, Lindbom LO, Angeby K, Florvall L: Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain. Eur J Pharmacol. 1984 Jul 20;102(3-4):459-74. [PubMed:6149133 ]
  4. Arnt J: Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine. Eur J Pharmacol. 1995 Sep 5;283(1-3):55-62. [PubMed:7498321 ]
  5. Huettl P, Gerhardt GA, Browning MD, Masserano JM: Effects of dopamine receptor agonists and antagonists on catecholamine release in bovine chromaffin cells. J Pharmacol Exp Ther. 1991 May;257(2):567-74. [PubMed:1674528 ]
  6. Nilsson CL, Ekman A, Hellstrand M, Eriksson E: Inverse agonism at dopamine D2 receptors. Haloperidol-induced prolactin release from GH4C1 cells transfected with the human D2 receptor is antagonized by R(-)-n-propylnorapomorphine, raclopride, and phenoxybenzamine. Neuropsychopharmacology. 1996 Jul;15(1):53-61. [PubMed:8797192 ]
  7. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [PubMed:17111172 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
References
  1. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [PubMed:17111172 ]
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. [PubMed: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. [PubMed:17016423 ]
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 activate adenylyl cyclase
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular weight:
49292.8
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: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. [PubMed:17016423 ]
  3. Cai G, Gurdal H, Smith C, Wang HY, Friedman E: Inverse agonist properties of dopaminergic antagonists at the D(1A) dopamine receptor: uncoupling of the D(1A) dopamine receptor from G(s) protein. Mol Pharmacol. 1999 Nov;56(5):989-96. [PubMed:10531405 ]
  4. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, Machulla HJ, Bares R, Glaser T, Wormstall H: Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology (Berl). 2007 Feb;190(2):241-9. Epub 2006 Nov 17. [PubMed:17111172 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular weight:
51420.4
References
  1. Golds PR, Przyslo FR, Strange PG: The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980 Mar;68(3):541-9. [PubMed:7052344 ]

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. Hait WN, Gesmonde JF, Murren JR, Yang JM, Chen HX, Reiss M: Terfenadine (Seldane): a new drug for restoring sensitivity to multidrug resistant cancer cells. Biochem Pharmacol. 1993 Jan 26;45(2):401-6. [PubMed:8094615 ]
  2. Dey S, Hafkemeyer P, Pastan I, Gottesman MM: A single amino acid residue contributes to distinct mechanisms of inhibition of the human multidrug transporter by stereoisomers of the dopamine receptor antagonist flupentixol. Biochemistry. 1999 May 18;38(20):6630-9. [PubMed:10350482 ]
  3. Hafkemeyer P, Licht T, Pastan I, Gottesman MM: Chemoprotection of hematopoietic cells by a mutant P-glycoprotein resistant to a potent chemosensitizer of multidrug-resistant cancers. Hum Gene Ther. 2000 Mar 1;11(4):555-65. [PubMed:10724034 ]
  4. Yang JM, Vassil A, Hait WN: Involvement of phosphatidylinositol-3-kinase in membrane ruffling induced by P-glycoprotein substrates in multidrug-resistant carcinoma cells. Biochem Pharmacol. 2002 Mar 1;63(5):959-66. [PubMed:11911848 ]
  5. Ford JM, Bruggemann EP, Pastan I, Gottesman MM, Hait WN: Cellular and biochemical characterization of thioxanthenes for reversal of multidrug resistance in human and murine cell lines. Cancer Res. 1990 Mar 15;50(6):1748-56. [PubMed:1968358 ]
  6. Ford JM, Yang JM, Hait WN: Effect of buthionine sulfoximine on toxicity of verapamil and doxorubicin to multidrug resistant cells and to mice. Cancer Res. 1991 Jan 1;51(1):67-72. [PubMed:1988108 ]