Identification

Name
Thiothixene
Accession Number
DB01623
Type
Small Molecule
Groups
Approved
Description

A thioxanthine used as an antipsychotic agent. Its effects are similar to the phenothiazine antipsychotics.

Structure
Thumb
Synonyms
  • cis-thiothixene
  • Thiothixene
  • Tiotixene
  • Tiotixeno
  • Tiotixenum
External IDs
CP-12252-1 / NSC-108165 / P-4657 B / P-4657B
Product Ingredients
IngredientUNIICASInChI Key
Thiothixene hydrochlorideB3CRJ1EWJU22189-31-7MEUAAEMCZUPORO-LRSHZYOCSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NavaneCapsule10 mg/1OralRoerig1967-07-242012-08-01Us
NavaneSolution, concentrate5 mg/1mLOralRoerig2006-12-072006-12-07Us
NavaneCapsule2 mg/1OralRoerig1967-07-242012-08-01Us
NavaneCapsule20 mg/1OralRoerig1967-07-242012-08-01Us
NavaneCapsule1 mg/1OralRoerig1967-07-242012-08-01Us
NavaneCapsule5 mg/1OralRoerig1967-07-242012-08-01Us
Navane Cap 2mgCapsule2 mgOralErfa Canada 2012 Inc1969-12-312015-06-05Canada
Navane Cap 5mgCapsule5 mgOralErfa Canada 2012 Inc1969-12-31Not applicableCanada
Navane Capsules 10mgCapsule10 mgOralErfa Canada 2012 Inc1969-12-312015-06-05Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThiothixeneCapsule5 mg/1OralRebel Distributors1987-06-24Not applicableUs
ThiothixeneCapsule1 mg/1OralRemedy Repack2017-11-09Not applicableUs
ThiothixeneCapsule2 mg/1OralRemedy Repack2011-08-172011-08-18Us
ThiothixeneCapsule5 mg/1OralMylan Pharmaceuticals Inc.1987-06-23Not applicableUs
ThiothixeneCapsule5 mg/1OralPhysicians Total Care, Inc.1993-02-172002-06-30Us
ThiothixeneCapsule5 mg/1OralREMEDYREPACK INC.2018-11-30Not applicableUs
ThiothixeneCapsule10 mg/1OralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
ThiothixeneCapsule2 mg/1OralSandoz1987-06-24Not applicableUs
ThiothixeneCapsule5 mg/1OralMylan Institutional1998-03-05Not applicableUs
ThiothixeneCapsule5 mg/1OralRemedy Repack2011-07-222011-07-23Us
International/Other Brands
Navan / Navaron / Orbinamon
Categories
UNII
7318FJ13YJ
CAS number
3313-26-6
Weight
Average: 443.625
Monoisotopic: 443.170118567
Chemical Formula
C23H29N3O2S2
InChI Key
GFBKORZTTCHDGY-UWVJOHFNSA-N
InChI
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-
IUPAC Name
(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide
SMILES
CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3\C2=C\CCN2CCN(C)CC2)C=C1

Pharmacology

Indication

For the management of schizophrenia.

Associated Conditions
Pharmacodynamics

Thiothixene is an antipsychotic of the thioxanthene series. Navane possesses certain chemical and pharmacological similarities to the piperazine phenothiazines and differences from the aliphatic group of phenothiazines. Although widely used in the treatment of schizophrenia for several decades, thiothixene is seldom used today in favor of atypical antipsychotics such as risperidone.

Mechanism of action

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).

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AD(1A) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
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 central nervous system depression, coma, difficulty swallowing, dizziness, drowsiness, head tilted to the side, low blood pressure, muscle twitching, rigid muscles, salivation, tremors, walking disturbances, and weakness.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Thiothixene.
2,5-Dimethoxy-4-ethylamphetamineThiothixene may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Thiothixene is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Thiothixene.
3,4-MethylenedioxyamphetamineThiothixene may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Thiothixene.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Thiothixene.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Thiothixene.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Thiothixene is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Thiothixene.
Food Interactions
  • Avoid alcohol

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015560
KEGG Drug
D00374
PubChem Compound
941651
PubChem Substance
46505564
ChemSpider
819430
BindingDB
78576
ChEBI
9571
ChEMBL
CHEMBL1201
Therapeutic Targets Database
DAP000318
PharmGKB
PA451669
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Thiothixene
ATC Codes
N05AF04 — Tiotixene
AHFS Codes
  • 28:16.08.32 — Thioxanthenes

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Comprehensive Consultant Services Inc.
  • Direct Dispensing Inc.
  • Heartland Repack Services LLC
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral20 mg/1
Solution, concentrateOral5 mg/1mL
CapsuleOral2 mg
CapsuleOral5 mg
CapsuleOral10 mg
CapsuleOral1 mg/1
CapsuleOral10 mg/1
CapsuleOral2 mg/1
CapsuleOral5 mg/1
Prices
Unit descriptionCostUnit
Navane 20 mg capsule3.15USD capsule
Navane 10 mg capsule1.66USD capsule
Navane 5 mg capsule1.2USD capsule
Navane 2 mg capsule0.8USD capsule
Thiothixene 10 mg capsule0.67USD capsule
Thiothixene 5 mg capsule0.47USD capsule
Thiothixene 2 mg capsule0.31USD capsule
Thiothixene 1 mg capsule0.24USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0139 mg/mLALOGPS
logP4.01ALOGPS
logP3.36ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.86 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity137.85 m3·mol-1ChemAxon
Polarizability50.35 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9969
Blood Brain Barrier+0.9437
Caco-2 permeable-0.6277
P-glycoprotein substrateSubstrate0.8707
P-glycoprotein inhibitor IInhibitor0.9247
P-glycoprotein inhibitor IIInhibitor0.9036
Renal organic cation transporterNon-inhibitor0.5373
CYP450 2C9 substrateNon-substrate0.7951
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.5269
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5406
Ames testNon AMES toxic0.651
CarcinogenicityNon-carcinogens0.8173
BiodegradationNot ready biodegradable0.947
Rat acute toxicity2.7586 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5093
hERG inhibition (predictor II)Non-inhibitor0.7259
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0000900000-6aa6254b49096ef09aad
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0000900000-5428adb371bd4bdc7b36
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000f-8389500000-52eb8fcb0fd8490f1c66
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-007a-4191000000-781e4a9b062cbb242a0c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00ds-2290000000-0fca1120c4649dbf4f61
MS/MS Spectrum - , positiveLC-MS/MSsplash10-007c-3593200000-8fe6b44b1210ffa933d1

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiopyrans
Sub Class
1-benzothiopyrans
Direct Parent
Thioxanthenes
Alternative Parents
Diarylthioethers / N-methylpiperazines / Organosulfonamides / Benzenoids / Aminosulfonyl compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Thioxanthene / Diarylthioether / Aryl thioether / N-alkylpiperazine / N-methylpiperazine / 1,4-diazinane / Piperazine / Organosulfonic acid amide / Benzenoid / Organic sulfonic acid or derivatives
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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]
  2. Xie C, Pogribna M, Word B, Lyn-Cook L Jr, Lyn-Cook BD, Hammons GJ: In vitro analysis of factors influencing CYP1A2 expression as potential determinants of interindividual variation. Pharmacol Res Perspect. 2017 Mar 2;5(2):e00299. doi: 10.1002/prp2.299. eCollection 2017 Apr. [PubMed:28357125]
  3. Thiothixene [Link]
  4. CYP1A2 cancer.gov document [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Kitamura K, Omran AA, Nagata C, Kamijima Y, Tanaka R, Takegami S, Kitade T: Effects of inorganic ions on the binding of triflupromazine and chlorpromazine to bovine serum albumin studied by spectrometric methods. Chem Pharm Bull (Tokyo). 2006 Jul;54(7):972-6. [PubMed:16819214]
  2. Rukhadze MD, Bezarashvili GS, Sidamonidze NS, Tsagareli SK: Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments. Biomed Chromatogr. 2001 Oct;15(6):365-73. [PubMed:11559920]
  3. Silva D, Cortez CM, Louro SR: Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Braz J Med Biol Res. 2004 Jul;37(7):963-8. Epub 2004 Jun 22. [PubMed:15264002]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Secondary active organic cation 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-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
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]

Drug created on August 29, 2007 14:17 / Updated on December 16, 2018 06:49