Flupenthixol (CED0006093)

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:52 UTC

Update Date

2026-05-14 16:51:23 UTC

SynCED ID

CED0006093

Secondary Accession Numbers

CHEM002294
T3D2920

Identification

Common Name

Flupenthixol

Class

Small Molecule

Description

Flupenthixol is an exogenous organic compound with the formula C23H27F3N2OS and an average molecular weight of 436.54 g/mol. It exists as a solid at room temperature. Flupenthixol belongs to the 1-benzothiopyrans, a subclass of benzothiopyrans within the organic compounds. This compound is utilized as a first generation antipsychotic, an antidepressant, and an anxiolytic drug. Biologically, it functions as a dopaminergic antagonist and an alpha-adrenergic antagonist, and it acts as a chemical inhibitor of EC 3.4.21.26 (prolyl oligopeptidase). Its antipsychotic activity is thought to be related to the blocking of postsynaptic dopamine receptors in the central nervous system. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, as well as an alpha-adrenergic receptor antagonist, although its full mechanism of action is not completely understood. Recorded protein targets include the D(1A) dopamine receptor (DRD1), D(2) dopamine receptor (DRD2), D(3) dopamine receptor (DRD3), Alpha-1A adrenergic receptor (ADRA1A), 5-hydroxytryptamine receptor 2A (HTR2A), Muscarinic acetylcholine receptor M1 (CHRM1), Sigma non-opioid intracellular receptor 1 (SIGMAR1), and ATP-dependent translocase ABCB1, among others. Flupenthixol is found in indoor air (air, dust & atmospheric transport) and in antipsychotics (healthcare, pharmaceuticals & veterinary products). Exposure routes for the compound include oral, intramuscular, and inhalation.

Contaminant Type

Amine
Antipsychotic Agent
Dopamine Antagonist
Drug
Ether
Human Neurotoxin
Metabolite
Organic Compound
Organofluoride
Synthetic Compound
Thioxanthene

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Not Available

Chemical Formula

C₂₃H₂₇F₃N₂OS

Average Molecular Mass

436.540 g/mol

Monoisotopic Mass

436.180 g/mol

CAS Registry Number

2709-56-0

IUPAC Name

2-(4-{3-[(9E)-2-(trifluoromethyl)-9,9a-dihydro-4aH-thioxanthen-9-ylidene]propyl}piperazin-1-yl)ethan-1-ol

Traditional Name

2-(4-{3-[(9E)-2-(trifluoromethyl)-4a,9a-dihydrothioxanthen-9-ylidene]propyl}piperazin-1-yl)ethanol

SMILES

[H]\C(CCN1CCN(CCO)CC1)=C1\C2C=C(C=CC2SC2=CC=CC=C12)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/b18-5-

InChI Key

DTTVNHWDONBIKE-DVZOWYKESA-N

Chemical Taxonomy

Description

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

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Applications

Biological Roles

Chemical Roles

EC 3.4.21.26 (prolyl oligopeptidase) inhibitor ?

Organoleptic Effects

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	0.000346 mg/ml

Predicted Properties

Property	Value	Source
Water Solubility	0.003 g/L	ALOGPS
logP	4.12	ALOGPS
logP	3.54	ChemAxon
logS	-5.2	ALOGPS
pKa (Strongest Acidic)	15.59	ChemAxon
pKa (Strongest Basic)	8.51	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	26.71 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	120.93 m³·mol⁻¹	ChemAxon
Polarizability	45.23 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-000i-0201900000-73ec21fa2c7fa423d80c	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0a4i-2937500000-df7eb8e76ec3519db844	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-010a-3901000000-9de441d4a43c6d405a24	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-000i-0000900000-ac8754cf6336195c2271	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-000i-1401900000-bee1aa4336a030e4209a	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0006-9201000000-bbbe4f3d1a218bd24204	Not Available	View Spectrum

Toxicity Profile

Toxicity Values

Toxicity Value	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Toxicity Rating	Reference
300.0 mk/kg	Mouse	LD50	Oral	experimental	Not Available	1
791.0 mg/kg	Rat	LD50	Oral	experimental	Not Available	1
87.0 mk/kg	Mouse	LD50	Intravenous	experimental	Not Available	1
37.0 mg/kg	Rat	LD50	Intravenous	experimental	Not Available	1
48.0 Log mg/kg [30:85]	Rat	LD50	oral	predicted	Not Available	Not Available

Toxicity / Toxin Class

Not Available

Mechanism of Toxicity

Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Minimum Risk Level

Not Available

Symptoms

Not Available

Treatment

Not Available

Health Effects

Health Effect	Relationship	Direction	Description	Reference

Exposure Sources

Source ID	Source	Sector	Reference
CEDs000019	Indoor air?Indoor air can be a significant reservoir for synthetic chemical contaminants, which often originate from various sources within enclosed environments.	Air, dust & atmospheric transport	Not Available
CEDs000374	Antipsychotics?Antipsychotics are a class of synthetic chemicals used primarily for the treatment of psychiatric disorders, including schizophrenia and bipolar disorder.	Healthcare, pharmaceuticals & veterinary products	Not Available
CEDs000518	Electrically Stimulated Smoking Devices?Electrically stimulated smoking devices, commonly known as e-cigarettes or vape pens, utilize electrical components to heat a liquid solution, often containing nicotine, flavorings, and other additives, to produce an aerosol for inhalation.	Electrical & Electronic Equipment	PubChem
CEDs000530	Radio Transmission Systems?Radio transmission systems utilize a variety of synthetic chemicals in their manufacturing and maintenance processes.	Electrical & Electronic Equipment	PubChem
CEDs000545	Food Preservation?Food preservation often involves the use of synthetic chemicals, such as preservatives, flavor enhancers, and color additives, to extend shelf life and enhance the sensory qualities of food products.	Food, food processing & cookware	PubChem
CEDs000549	Preparation Of Wine Or Sparkling Wine?The preparation of wine or sparkling wine involves various stages, including fermentation, aging, and bottling, which can introduce potential sources of synthetic chemical contamination.	Food, food processing & cookware	PubChem
CEDs000559	Non Electric Simulated Smoking Devices?Non-electric simulated smoking devices, often designed to mimic the experience of smoking without combustion, can be sources of synthetic chemical contamination due to the materials and chemicals used in their construction and operation.	Household cleaning & consumer products	PubChem
CEDs000561	Perfumes Within Detergents And Soaps?Perfumes within detergents and soaps are synthetic fragrance compounds added to enhance the sensory experience of cleaning products.	Household cleaning & consumer products	PubChem
CEDs000580	Manufacture Preparation Of Tobacco Products?The manufacture and preparation of tobacco products involve various processes that can result in the introduction of synthetic chemicals into the environment.	Industrial manufacturing & chemical processing	PubChem
CEDs000611	Anti Perspirants Or Body Deoderants?Antiperspirants and body deodorants commonly contain synthetic chemicals such as aluminum compounds, parabens, and synthetic fragrances.	Personal care & cosmetics	PubChem
CEDs000632	Apparel?Apparel production often involves the use of various synthetic chemicals, including dyes, finishing agents, and preservatives.	Textiles, leather & furnishings	PubChem
CEDs000642	Footwear?Footwear production often involves the use of various synthetic chemicals, such as adhesives, dyes, and treatments, which can contribute to environmental contamination.	Textiles, leather & furnishings	PubChem
CEDs000671	Airplanes And Helicopters?Airplanes and helicopters are significant sources of synthetic chemical contamination primarily through the use of aviation fuels, lubricants, and de-icing agents.	Aviation & Aerospace	PubChem
CEDs000685	Ceramics?Ceramics can be a source of synthetic chemical contamination through various additives and processing agents used in their production.	Building & Construction	PubChem
CEDs000696	Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.	Industrial manufacturing & chemical processing	PubChem
CEDs000727	Printing Machines Or Presses?Printing machines or presses commonly utilize synthetic chemicals such as inks, solvents, and cleaning agents.	Paper, pulp & fiber products	PubChem
CEDs000735	Explosives?Explosives are chemical compounds or mixtures designed to undergo rapid decomposition, releasing energy in the form of gas and heat.	Defense & military infrastructure	PubChem
CEDs000741	Pigment Pastes?Pigment pastes are concentrated dispersions of pigments used to impart color and properties to materials.	Paper, pulp & fiber products	PubChem
CEDs000744	Water, Wastewater, & Sewage Treatment?Water, wastewater, and sewage treatment processes are critical for managing and mitigating pollutants in water systems.	Wastewater, sanitation & biosolids	PubChem

Pathways

3 pathwaysPathway Source: PathBank

Flupentixol Dopamine Antagonist Action Pathway

Flupentixol Serotonin Antagonist Action Pathway

Flupentixol Drug Metabolism Action Pathway

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	Sigma non-opioid intracellular receptor 1	Q99720	Humans	Predicted (SEA)	Prediction Confidence Score 0.368 Applicability Domain 0.478 Statistical Significance 0.0197 Supporting Reference Compounds 562 E-value 153.207
Click to view 3D structure	D(1A) dopamine receptor	P18901	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.332 Applicability Domain 0.478 Statistical Significance 0.0133 Supporting Reference Compounds 206 E-value 103.695
Click to view 3D structure	5-hydroxytryptamine receptor 6	P50406	Humans	Predicted (SEA)	Prediction Confidence Score 0.295 Applicability Domain 0.412 Statistical Significance 0.0508 Supporting Reference Compounds 536 E-value 395.63
Click to view 3D structure	Delta-type opioid receptor	P41143	Humans	Predicted (SEA)	Prediction Confidence Score 0.284 Applicability Domain 0.478 Statistical Significance 0.0757 Supporting Reference Compounds 427 E-value 589.63
Click to view 3D structure	Voltage-gated inwardly rectifying potassium channel KCNH2	Q12809	Humans	Predicted (SEA)	Prediction Confidence Score 0.28 Applicability Domain 0.347 Statistical Significance 0.2692 Supporting Reference Compounds 1498 E-value 2095.78
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P19327	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.274 Applicability Domain 0.347 Statistical Significance 0.0972 Supporting Reference Compounds 541 E-value 756.617
Click to view 3D structure	D(2) dopamine receptor	P14416	Humans	Predicted (SEA)	Prediction Confidence Score 0.273 Applicability Domain 0.347 Statistical Significance 0.1651 Supporting Reference Compounds 1103 E-value 1285.13
Click to view 3D structure	5-hydroxytryptamine receptor 7	P34969	Humans	Predicted (SEA)	Prediction Confidence Score 0.271 Applicability Domain 0.347 Statistical Significance 0.1003 Supporting Reference Compounds 565 E-value 780.516
Click to view 3D structure	Alpha-2A adrenergic receptor	P08913	Humans	Predicted (SEA)	Prediction Confidence Score 0.268 Applicability Domain 0.347 Statistical Significance 0.0969 Supporting Reference Compounds 487 E-value 754.67
Click to view 3D structure	Protein deacetylase HDAC6	Q9UBN7	Humans	Predicted (SEA)	Prediction Confidence Score 0.264 Applicability Domain 0.412 Statistical Significance 0.1856 Supporting Reference Compounds 553 E-value 1444.57
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P08908	Humans	Predicted (SEA)	Prediction Confidence Score 0.263 Applicability Domain 0.347 Statistical Significance 0.1835 Supporting Reference Compounds 953 E-value 1428.92
Click to view 3D structure	5-hydroxytryptamine receptor 2A	P28223	Humans	Predicted (SEA)	Prediction Confidence Score 0.262 Applicability Domain 0.347 Statistical Significance 0.2117 Supporting Reference Compounds 955 E-value 1648.07
Click to view 3D structure	5-hydroxytryptamine receptor 2C	P28335	Humans	Predicted (SEA)	Prediction Confidence Score 0.261 Applicability Domain 0.347 Statistical Significance 0.1942 Supporting Reference Compounds 823 E-value 1511.6
Click to view 3D structure	D(3) dopamine receptor	P35462	Humans	Predicted (SEA)	Prediction Confidence Score 0.26 Applicability Domain 0.347 Statistical Significance 0.193 Supporting Reference Compounds 861 E-value 1502.65
Click to view 3D structure	Pleiotropic ABC efflux transporter of multiple drugs	P33302	Saccharomyces cerevisiae S288c	Predicted (SEA)	Prediction Confidence Score 0.26 Applicability Domain 0.347 Statistical Significance 0.0013 Supporting Reference Compounds 10 E-value 9.9647
Click to view 3D structure	D(4) dopamine receptor	P21917	Humans	Predicted (SEA)	Prediction Confidence Score 0.258 Applicability Domain 0.347 Statistical Significance 0.1618 Supporting Reference Compounds 524 E-value 1259.44
Click to view 3D structure	Potassium channel subfamily K member 2	O95069	Humans	Predicted (SEA)	Prediction Confidence Score 0.257 Applicability Domain 0.478 Statistical Significance 0.0017 Supporting Reference Compounds 21 E-value 13.4679
Click to view 3D structure	D(1A) dopamine receptor	P21728	Humans	Predicted (SEA)	Prediction Confidence Score 0.256 Applicability Domain 0.347 Statistical Significance 0.1203 Supporting Reference Compounds 425 E-value 936.37
Click to view 3D structure	D(2) dopamine receptor	P61169	Rat	Predicted (SEA)	Prediction Confidence Score 0.256 Applicability Domain 0.276 Low confidence Statistical Significance 0.148 Supporting Reference Compounds 528 E-value 1151.86
Click to view 3D structure	Muscarinic acetylcholine receptor M1	P11229	Humans	Predicted (SEA)	Prediction Confidence Score 0.253 Applicability Domain 0.347 Statistical Significance 0.1307 Supporting Reference Compounds 385 E-value 1017.26
Click to view 3D structure	Muscarinic acetylcholine receptor M2	P08172	Humans	Predicted (SEA)	Prediction Confidence Score 0.253 Applicability Domain 0.347 Statistical Significance 0.1251 Supporting Reference Compounds 373 E-value 973.738
Click to view 3D structure	Muscarinic acetylcholine receptor M4	P08173	Humans	Predicted (SEA)	Prediction Confidence Score 0.253 Applicability Domain 0.347 Statistical Significance 0.098 Supporting Reference Compounds 297 E-value 762.845
Click to view 3D structure	Alpha-1A adrenergic receptor	P43140	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.252 Applicability Domain 0.347 Statistical Significance 0.0776 Supporting Reference Compounds 208 E-value 604.266
Click to view 3D structure	Muscarinic acetylcholine receptor M3	P20309	Humans	Predicted (SEA)	Prediction Confidence Score 0.251 Applicability Domain 0.347 Statistical Significance 0.1105 Supporting Reference Compounds 310 E-value 860.39
Click to view 3D structure	Histamine H1 receptor	P35367	Humans	Predicted (SEA)	Prediction Confidence Score 0.251 Applicability Domain 0.347 Statistical Significance 0.188 Supporting Reference Compounds 507 E-value 1463.25
Click to view 3D structure	D(2) dopamine receptor	P14416	Humans	Known	Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.
Click to view 3D structure	ATP-dependent translocase ABCB1	P08183	Humans	Known	Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.
Click to view 3D structure	D(1A) dopamine receptor	P21728	Humans	Known	Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.
Click to view 3D structure	Alpha-1A adrenergic receptor	P35348	Humans	Known	Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.
Click to view 3D structure	5-hydroxytryptamine receptor 2A	P28223	Humans	Known	Not Available
Click to view 3D structure	Muscarinic acetylcholine receptor M1	P11229	Humans	Known	Not Available
Click to view 3D structure	Neuron-specific vesicular protein calcyon	Q9NYX4	Humans	Known	Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.
Click to view 3D structure	Sigma non-opioid intracellular receptor 1	Q99720	Humans	Known	Not Available

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Not Available

Chemspider ID

Not Available

ChEBI ID

Not Available

PubChem Compound ID

25137855

Kegg Compound ID

Not Available

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Smith Kline & French Laboratories; British Patent 925,538; May 8, 1963.
Craig, P.N. and Zirkle, C.L.; U.S. Patent 3,282,930; November 1, 1966; assigned to Smith Kline & French Laboratories.

MSDS

Not Available

General References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [PubMed: 18048412]
Drugs.com - http://www.drugs.com/cons/Flupenthixol.html

Flupenthixol (CED0006093)

Structure for CHEM002294: Flupenthixol

Structure