Identification

Name
Triflupromazine
Accession Number
DB00508  (APRD00465)
Type
Small Molecule
Groups
Approved, Vet approved
Description

A phenothiazine used as an antipsychotic agent and as an antiemetic. [PubChem]

Structure
Thumb
Synonyms
  • 10-(3-(Dimethylamino)propyl)-2-(trifluoromethyl)phenothiazine
  • 2-(Trifluoromethyl)promazine
  • 2-Trifluoromethyl-10-(gamma-dimethylaminopropyl)phenothiazine
  • Fluopromazine
  • Triflupromazin
  • Triflupromazina
  • Triflupromazine
  • Triflupromazinum
External IDs
MC 4703 / SKF 4648-A
Product Ingredients
IngredientUNIICASInChI Key
Triflupromazine Hydrochloride9E75N4A5HM1098-60-8FTNWXGFYRHWUKG-UHFFFAOYSA-N
International/Other Brands
Vesprin (Bristol Myers Squibb)
Categories
UNII
RO16TQF95Y
CAS number
146-54-3
Weight
Average: 352.417
Monoisotopic: 352.122103923
Chemical Formula
C18H19F3N2S
InChI Key
XSCGXQMFQXDFCW-UHFFFAOYSA-N
InChI
InChI=1S/C18H19F3N2S/c1-22(2)10-5-11-23-14-6-3-4-7-16(14)24-17-9-8-13(12-15(17)23)18(19,20)21/h3-4,6-9,12H,5,10-11H2,1-2H3
IUPAC Name
dimethyl({3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl})amine
SMILES
CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(C=C2)C(F)(F)F

Pharmacology

Indication

Used mainly in the management of psychoses. Also used to control nausea and vomiting.

Pharmacodynamics

Triflupromazine is a member of a class of drugs called phenthiazines, which are dopamine D1/D2 receptor antagonists. Phenothiazines are used to treat serious mental and emotional disorders, including schizophrenia and other psychotic disorders. It reduces anxiety, emotional withdrawal, hallucinations, disorganized thoughts, blunted mood, and suspiciousness. Triflupromazine is used particularly to control violent behavior during acute episodes of psychotic disorders. It can also be used to control severe nausea and vomiting, severe hiccups, and moderate to severe pain in some hospitalized patients. Triflupromazine acts on the central nervous system.

Mechanism of action

Triflupromazine binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone (CTZ) and vomiting centre. Triflupromazine blocks the neurotransmitter dopamine and the vagus nerve in the gastrointestinal tract. Triflupromazine also binds the muscarinic acetylcholine receptors (M1 and M2) and the tryptamine D receptors (5HT2B).

TargetActionsOrganism
AD(1A) dopamine receptor
antagonist
Human
AD(2) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2B
antagonist
Human
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M2
antagonist
Human
Absorption

Absorption may be erratic and peak plasma concentrations show large interindividual differences.

Volume of distribution
Not Available
Protein binding

Very high (90% or more).

Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, and restlessness.

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineTriflupromazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineTriflupromazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineTriflupromazine may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineTriflupromazine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
5'-Deoxy-5'-MethylthioadenosineThe serum concentration of Triflupromazine can be increased when it is combined with 5'-Deoxy-5'-Methylthioadenosine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Triflupromazine is combined with 7-Nitroindazole.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Triflupromazine.
AcepromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Aceprometazine.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Triflupromazine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014650
KEGG Drug
D00390
PubChem Compound
5568
PubChem Substance
46507344
ChemSpider
5367
BindingDB
67544
ChEBI
9711
ChEMBL
CHEMBL570
Therapeutic Targets Database
DAP000294
PharmGKB
PA451773
IUPHAR
4330
Guide to Pharmacology
GtP Drug Page
Wikipedia
Triflupromazine
ATC Codes
N05AA05 — Triflupromazine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP5.54BIOBYTE (1995)
logS-5.3ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0018 mg/mLALOGPS
logP4.95ALOGPS
logP4.81ChemAxon
logS-5.3ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity94.93 m3·mol-1ChemAxon
Polarizability35.29 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9926
Blood Brain Barrier+0.9839
Caco-2 permeable+0.7847
P-glycoprotein substrateSubstrate0.7862
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.8737
Renal organic cation transporterInhibitor0.6721
CYP450 2C9 substrateNon-substrate0.7813
CYP450 2D6 substrateSubstrate0.5115
CYP450 3A4 substrateSubstrate0.5822
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9141
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.8156
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6166
Ames testNon AMES toxic0.875
CarcinogenicityNon-carcinogens0.9349
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.2485 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9849
hERG inhibition (predictor II)Inhibitor0.8433
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.91 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-9013000000-ef47630a3d0764a3497f
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-3019000000-dc3f041820258623fda5
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9121000000-0dfbd5aaf88b987dbe84
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / Benzenoids / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organofluorides / Hydrocarbon derivatives / Alkyl fluorides
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Para-thiazine / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Thioether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, organofluorine compound, tertiary amine (CHEBI:9711)

Targets

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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Cooper M, Wyllie JH: Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85. [PubMed:497523]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Snyder S, Greenberg D, Yamamura HI: Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry. 1974 Jul;31(1):58-61. [PubMed:4152054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Snyder S, Greenberg D, Yamamura HI: Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry. 1974 Jul;31(1):58-61. [PubMed:4152054]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Muraoka S, Miura T: Inactivation of cholinesterase induced by chlorpromazine cation radicals. Pharmacol Toxicol. 2003 Feb;92(2):100-4. [PubMed:12747580]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ibrahim S, Peggins J, Knapton A, Licht T, Aszalos A: Influence of antipsychotic, antiemetic, and Ca(2+) channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation. J Pharmacol Exp Ther. 2000 Dec;295(3):1276-83. [PubMed:11082465]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:47