THIOTHIXENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H29N3O2S2
Molecular Weight	443.625
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3\C2=C\CCN4CCN(C)CC4)C=C1

InChI

InChIKey=GFBKORZTTCHDGY-UWVJOHFNSA-N

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-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1145194 | (1977) Annual Reports in Medicinal Chemistry, v.12, page 255, retrieved from: https://books.google.ru/books?id=1KgRHPGu7LEC | https://www.ncbi.nlm.nih.gov/pubmed/7161337https://www.drugs.com/ppa/thiothixene.html
Curator's Comment: Description was created based on several sources, including http://www.pfizer.com/files/products/uspi_navane.pdf | http://www.psychatlanta.com/psychatlanta/wp-content/uploads/navane.pdf | http://pubs.rsc.org/EN/content/articlelanding/1967/c1/c1967000743b#!divAbstract

Thiothixene (trade mark Navane) belongs to a class of antipsychotics known as the first-generation antipsychotics, sometimes referred to as conventional or typical antipsychotics. Thiothixene is a thioxanthene antipsychotic which elicits antipsychotic activity by postsynaptic blockade of CNS dopamine receptors resulting in inhibition of dopamine-mediated effects; also has alpha-adrenergic blocking activity. Thiothixene is effective in the management of schizophrenia. Only cis isomer of thiothixene exerts clinical effectivity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
dopamine secretion 11 Target ID: GO:0014046 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1145194	Inhibitor 8297
Dopamine receptor 60 Target ID: CHEMBL2096970 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1060143	Binding Agent 1064	22.0 µM [IC50]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: http://www.genome.jp/dbget-bin/www_bget?D00374+D02612 \| https://www.drugbank.ca/drugs/DB01623#targets	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: http://www.pfizer.com/files/products/uspi_navane.pdf	Primary		Approved 8429	NAVANE Approved Use Thiothixene capsules are effective in the management of schizophrenia. Thiothixene capsules have not been evaluated in the management of behavioral complications in patients with mental retardation. Launch Date 1967
Unknown 2578

C_max

Value	Dose	Co-administered	Analyte	Population
27.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9447478	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		THIOTHIXENE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
117 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9447478	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		THIOTHIXENE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9447478	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		THIOTHIXENE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy, Elderly Patients Health Status: unhealthy Condition: Dementia-Related Psychosis Age Group: Elderly Patients Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
60 mg 1 times / day multiple, oral Highest studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	Disc. AE: Hyperprolactinemia, Menstrual irregularity... AEs leading to discontinuation/dose reduction: Hyperprolactinemia Menstrual irregularity Breast enlargement Amenorrhea Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	Disc. AE: Tardive dyskinesia, Neutropenia... AEs leading to discontinuation/dose reduction: Tardive dyskinesia Neutropenia (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf

AEs

AE	Significance	Dose	Population
Death	Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy, Elderly Patients Health Status: unhealthy Condition: Dementia-Related Psychosis Age Group: Elderly Patients Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
Amenorrhea	Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
Breast enlargement	Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
Hyperprolactinemia	Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
Menstrual irregularity	Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
Tardive dyskinesia	Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf
Neutropenia	severe Disc. AE	20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf	unhealthy Health Status: unhealthy Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016584s059lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1891	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/27/9/1078.long	yes [Ki 65 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336924/	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-055249	http://www.3bsc.com/index/pro_info.php?id=93728
AA Blocks	AA003APY	https://www.aablocks.com/goods/Goods/detail?id=AA003APY
AHH Chemical co.,ltd	MT-49407	http://www.ahhchemical.com/product/MT-49407.html
Alfa Chemistry	AP3313266	https://reagents.alfa-chemistry.com/product/thiothixene-cas-3313-26-6-10093.html
Aurora Fine Chemicals LLC	A17.877.865	http://online.aurorafinechemicals.com/info?ID=A17.877.865
BLD Pharm	BD121796	http://www.bldpharm.com/products/3313-26-6.html
CSNpharm	CSN21566	https://www.csnpharm.com/products/(z)-thiothixene.html
Chem Scene	CS-7959	http://www.chemscene.com/3313-26-6.html
ChemMol	49411943	http://www.chemmol.com/chemmol/49411943.html
ChemMol	99082728	http://www.chemmol.com/chemmol/99082728.html
Chemspace	CSSB00020677860	https://chem-space.com/CSSB00020677860
LGC Standards	LGCFOR3269.00	https://www.lgcstandards.com/US/en/p/LGCFOR3269.00
LGC Standards	MM3269.00	https://www.lgcstandards.com/US/en/p/MM3269.00
Lab Network	LN01312553	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01312553
MedChem Express	HY-108324	https://www.medchemexpress.com/_Z_-Thiothixene.html
Sigma-Aldrich	T4937_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/t4937?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1665003_USP	https://www.sigmaaldrich.com/catalog/product/usp/1665003?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S545259	http://www.smolecule.com/products/s545259
Smolecule	S583328	https://www.smolecule.com/products/s583328
THE BioTek	bt-284641	https://www.thebiotek.com/product/inhibitors/bt-284641
THE BioTek	bt-292946	https://www.thebiotek.com/product/others/bt-292946
Tyger Scientific	T15560	http://www.tygersci.com/phtml/3313-26-6.htm
abcr GmbH	AB154516	http://www.abcr.com/shop/en/AB154516
eNovation Chemicals	D590248	https://www.enovationchem.com/ProductDetails.asp?ProductID=D590248

PubMed

Title	Date	PubMed
Subjective response to antipsychotic drugs.	1981 Feb	7212946
Thiothixene plasma levels and clinical response in acute schizophrenia.	1981 May	7217026
Separation and quantitation of cis- and trans-thiothixene in human plasma by high-performance liquid chromatography.	1982 Dec 10	7161337
Psychopharmacological correlates of post-psychotic depression: a double-blind investigation of haloperidol vs thiothixene in outpatient schizophrenia.	1982 Mar	7037757
Neurotoxicity in patients with schizophrenia during lithium therapy.	1982 May-Jun	6123407
Neuroleptic malignant syndrome and malignant hyperthermia.	1983 Jan 29	6130277
Maprotiline hydrochloride associated with a clinical state of catatonic stupor and epileptic encephalogram.	1984 Aug	6470193
Drug interactions on spontaneous locomotor activity in rats. Neuroleptics and amphetamine-induced hyperactivity.	1984 Aug	6148710
Improved high-performance liquid chromatographic method for the quantitation of cis-thiothixene in plasma samples using trans-thiothixene as internal standard.	1984 Nov 28	6520191
Manic syndrome associated with zidovudine treatment.	1988 Jun 17	3163740
On the selection of mice for haloperidol response and non-response.	1991	1827527
Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1.	1997 May 3	9176928
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Density functional theory study of structural and electronic properties of trans and cis structures of thiothixene as a nano-drug.	2017 Nov 25	29177682

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Unknown

Name

Type

Language

THIOTHIXENE

Official Name

English

THIOTHIXENE [ORANGE BOOK]

Common Name

English

P-4657 B

Code

English

THIOTHIXENE [USAN]

Common Name

English

P-4657B

Code

English

THIOTHIXENE [USP-RS]

Common Name

English

(Z)-THIOTHIXENE

Common Name

English

TIOTIXENE

Official Name

English

tiotixene [INN]

Common Name

English

THIOTHIXENE [VANDF]

Common Name

English

(Z)-N,N-DIMETHYL-9-(3-(4-METHYL-1-PIPERAZINYL)PROPYLIDENE)THIOXANTHENE-2-SULFONAMIDE

Systematic Name

English

NAVANE

Brand Name

English

CP-12252-1

Code

English

THIOTHIXENE [USP MONOGRAPH]

Common Name

English

N,N-Dimethyl-9-[3-(4-methyl-1-piperazinyl)propylidene]thioxanthene-2-sulfonamide

Systematic Name

English

NSC-108165

Code

English

CIS-THIOTHIXENE

Common Name

English

TIOTIXENE [JAN]

Common Name

English

TIOTIXENE [MART.]

Common Name

English

THIOTHIXENE CIS-ISOMER [MI]

Common Name

English

ORBINAMON

Brand Name

English

9H-THIOXANTHENE-2-SULFONAMIDE, N,N-DIMETHYL-9-(3-(4-METHYL-1-PIPERAZINYL)PROPYLIDENE)-, (Z)-

Systematic Name

English

Tiotixene [WHO-DD]

Common Name

English

THIOTHIXENE [MI]

Common Name

English

Classification Tree Code System Code

LIVERTOX

956