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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2017-12-07 02:51:48 UTC
HMDB IDHMDB0015560
Secondary Accession Numbers
  • HMDB15560
Metabolite Identification
Common NameThiothixene
DescriptionThiothixene is only found in individuals that have used or taken this drug. It is a thioxanthine used as an antipsychotic agent. Its effects are similar to the phenothiazine antipsychotics. [PubChem]Thiothixene acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).
Structure
Thumb
Synonyms
ValueSource
TiotixeneKegg
NavaneKegg
(e)-ThiothixeneHMDB
cis-ThiothixeneHMDB
ThiothixineHMDB
Pfizer brand OF tiotixene dihydrochlorideMeSH
Pfizer brand OF tiotixeneMeSH
Tiotixene pfizer brandMeSH
Chemical FormulaC23H29N3O2S2
Average Molecular Weight443.625
Monoisotopic Molecular Weight443.170118567
IUPAC Name(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide
Traditional Namethiothixene
CAS Registry Number5591-45-7
SMILES
CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3\C2=C\CCN2CCN(C)CC2)C=C1
InChI Identifier
InChI=1S/C23H29N3O2S2/c1-24(2)30(27,28)18-10-11-23-21(17-18)19(20-7-4-5-9-22(20)29-23)8-6-12-26-15-13-25(3)14-16-26/h4-5,7-11,17H,6,12-16H2,1-3H3/b19-8-
InChI KeyGFBKORZTTCHDGY-UWVJOHFNSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassBenzothiopyrans
Direct ParentThioxanthenes
Alternative Parents
Substituents
  • Thioxanthene
  • Diarylthioether
  • Aryl thioether
  • N-alkylpiperazine
  • N-methylpiperazine
  • 1,4-diazinane
  • Piperazine
  • Organosulfonic acid amide
  • Benzenoid
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Sulfonyl
  • Aminosulfonyl compound
  • Tertiary amine
  • Tertiary aliphatic amine
  • Azacycle
  • Thioether
  • Amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Cell and elements:

Role

Industrial application:

  Pharmaceutical industry:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.014 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.014 g/LALOGPS
logP4.01ALOGPS
logP3.36ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.86 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity137.85 m³·mol⁻¹ChemAxon
Polarizability50.35 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, Positivesplash10-01p7-9308200000-52b945dc901ba41a91c7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-007c-3593200000-8fe6b44b1210ffa933d1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0000900000-6aa6254b49096ef09aadView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0000900000-5428adb371bd4bdc7b36View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000f-8389500000-52eb8fcb0fd8490f1c66View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-007a-4191000000-781e4a9b062cbb242a0cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00ds-2290000000-0fca1120c4649dbf4f61View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-007c-3593200000-8fe6b44b1210ffa933d1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0103900000-bf4826507276fd0fab3dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0f6y-0419300000-b640f1110ae72a7103a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-059i-9373000000-ad0d17f5724d06ea5fadView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0000900000-a2afb567b8b4ddb67d36View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0005-9207800000-429adb5832ee1e8650c0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052g-9200000000-c85846b09b6835e58111View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
NameSMPDB/PathwhizKEGG
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01623 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01623 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01623
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID819430
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkThiothixene
METLIN IDNot Available
PubChem Compound941651
PDB IDNot Available
ChEBI ID309829
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed: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. Shultz PJ, Sedor JR, Abboud HE: Dopaminergic stimulation of cAMP accumulation in cultured rat mesangial cells. Am J Physiol. 1987 Aug;253(2 Pt 2):H358-64. [PubMed:3039860 ]
  2. Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. [PubMed:11103886 ]
  3. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706 ]
  4. Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. [PubMed:15694263 ]
  5. Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. [PubMed:16867246 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [PubMed:20643630 ]
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. Kusumi I, Takahashi Y, Suzuki K, Kameda K, Koyama T: Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain. J Neural Transm (Vienna). 2000;107(3):295-302. [PubMed:10821438 ]
  2. Yamada J, Sugimoto Y, Horisaka K: Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. Biol Pharm Bull. 1995 Nov;18(11):1580-3. [PubMed:8593484 ]
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. Shultz PJ, Sedor JR, Abboud HE: Dopaminergic stimulation of cAMP accumulation in cultured rat mesangial cells. Am J Physiol. 1987 Aug;253(2 Pt 2):H358-64. [PubMed:3039860 ]
  2. Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. [PubMed:7918347 ]

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular weight:
61187.4
References
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [PubMed:12606755 ]