Thiothixene

Identification

Summary

Thiothixene is an antipsychotic indicated for the management of schizophrenia.

Brand Names
Navane
Generic Name
Thiothixene
DrugBank Accession Number
DB01623
Background

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

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 443.625
Monoisotopic: 443.170118567
Chemical Formula
C23H29N3O2S2
Synonyms
  • cis-thiothixene
  • Thiothixene
  • Tiotixene
  • Tiotixeno
  • Tiotixenum
External IDs
  • CP-12252-1
  • NSC-108165
  • P-4657 B
  • P-4657B

Pharmacology

Indication

For the management of schizophrenia.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofSchizophrenia••••••••••••
Contraindications & Blackbox Warnings
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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
ADopamine D2 receptor
antagonist
Humans
ADopamine D1 receptor
antagonist
Humans
U5-hydroxytryptamine receptor 2A
antagonist
Humans
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

Adverse Effects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Thiothixene is combined with 1,2-Benzodiazepine.
AbametapirThe serum concentration of Thiothixene can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Thiothixene can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Thiothixene can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Thiothixene can be decreased when combined with Acenocoumarol.
Food Interactions
  • Avoid alcohol.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Thiothixene hydrochlorideB3CRJ1EWJU22189-31-7MEUAAEMCZUPORO-LRSHZYOCSA-N
International/Other Brands
Navan / Navaron / Orbinamon
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NavaneCapsule10 mg/1OralRoerig1967-07-242012-08-01US flag
NavaneCapsule1 mg/1OralRoerig1967-07-242012-08-01US flag
NavaneCapsule5 mgOralSearchlight Pharma Inc1969-12-31Not applicableCanada flag
NavaneSolution, concentrate5 mg/1mLOralRoerig2006-12-072006-12-07US flag
NavaneCapsule5 mg/1OralRoerig1967-07-242012-08-01US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ThiothixeneCapsule5 mg/1OralREMEDYREPACK INC.2007-05-162018-06-25US flag
ThiothixeneCapsule10 mg/1OralPhysicians Total Care, Inc.1993-03-042002-06-30US flag
ThiothixeneCapsule5 mg/1OralNovitium Pharma Llc2019-04-05Not applicableUS flag
ThiothixeneCapsule2 mg/1OralREMEDYREPACK INC.2010-12-152018-03-21US flag
ThiothixeneCapsule5 mg/1OralRebel Distributors1987-06-24Not applicableUS flag

Categories

ATC Codes
N05AF04 — Tiotixene
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,4-diazinane / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Diarylthioether / Hydrocarbon derivative / N-alkylpiperazine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
7318FJ13YJ
CAS number
3313-26-6
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

References

General References
Not Available
Human Metabolome Database
HMDB0015560
KEGG Drug
D00374
PubChem Compound
941651
PubChem Substance
46505564
ChemSpider
819430
BindingDB
78576
RxNav
10510
ChEBI
9571
ChEMBL
CHEMBL1201
ZINC
ZINC000030690433
Therapeutic Targets Database
DAP000318
PharmGKB
PA451669
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tiotixene

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychosis / Schizoaffective Disorders / Schizophrenia / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableSchizophrenia1

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
CapsuleOral1 mg/1
CapsuleOral20 mg/1
CapsuleOral5 mg
Solution, concentrateOral5 mg/1mL
CapsuleOral2 mg
CapsuleOral10 mg
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)8.16Chemaxon
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-MSsplash10-01p7-9308200000-52b945dc901ba41a91c7
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-007c-3593200000-8fe6b44b1210ffa933d1
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
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0000900000-0dcec3a1cbb98563abe4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0004900000-83a28b9a623e20acebb8
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0007-0016900000-f05328e8f708a12cbbce
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000g-0149500000-28a31cc1860ad3cf3692
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00mp-1519600000-f1862b7aaa96487d63d6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-074i-1109100000-26b9855927f9cac76de0
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-227.1014217
predicted
DarkChem Lite v0.1.0
[M-H]-223.2769217
predicted
DarkChem Lite v0.1.0
[M-H]-201.6591
predicted
DeepCCS 1.0 (2019)
[M+H]+227.3568217
predicted
DarkChem Lite v0.1.0
[M+H]+222.6235217
predicted
DarkChem Lite v0.1.0
[M+H]+204.05466
predicted
DeepCCS 1.0 (2019)
[M+Na]+226.9817217
predicted
DarkChem Lite v0.1.0
[M+Na]+223.5196217
predicted
DarkChem Lite v0.1.0
[M+Na]+209.98012
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  3. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [Article]
  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. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [Article]
  2. Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL: H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology. 2003 Mar;28(3):519-26. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. Shin JG, Soukhova N, Flockhart DA: Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab Dispos. 1999 Sep;27(9):1078-84. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
  2. Thiothixene [Link]
  3. CYP1A2 cancer.gov document [File]

Carriers

Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
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. [Article]

Drug created at August 29, 2007 20:17 / Updated at March 18, 2024 16:48