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Identification
NameTriflupromazine
Accession NumberDB00508  (APRD00465)
TypeSmall Molecule
GroupsApproved, 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 Identifiers
  • MC 4703
  • SKF 4648-A
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
VesprinBristol Myers Squibb
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Triflupromazine Hydrochloride
ThumbNot applicableDBSALT001039
Categories
UNIIRO16TQF95Y
CAS number146-54-3
WeightAverage: 352.417
Monoisotopic: 352.122103923
Chemical FormulaC18H19F3N2S
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Benzenoid
  • Para-thiazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed mainly in the management of psychoses. Also used to control nausea and vomiting.
PharmacodynamicsTriflupromazine 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 actionTriflupromazine 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).
Related Articles
AbsorptionAbsorption may be erratic and peak plasma concentrations show large interindividual differences.
Volume of distributionNot Available
Protein bindingVery high (90% or more).
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.91 KB)
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0a4i-9121000000-0dfbd5aaf88b987dbe84View in MoNA
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesN05AA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Triflupromazine.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Triflupromazine.
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Triflupromazine.
AmphetamineTriflupromazine may decrease the stimulatory activities of Amphetamine.
BenzphetamineTriflupromazine may decrease the stimulatory activities of Benzphetamine.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Triflupromazine.
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Triflupromazine.
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Triflupromazine.
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Triflupromazine.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Triflupromazine.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Triflupromazine.
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Triflupromazine.
DextroamphetamineTriflupromazine may decrease the stimulatory activities of Dextroamphetamine.
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Triflupromazine.
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Triflupromazine.
DonepezilDonepezil may increase the central neurotoxic activities of Triflupromazine.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Triflupromazine.
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Triflupromazine.
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Triflupromazine.
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Triflupromazine.
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Triflupromazine.
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Triflupromazine.
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Triflupromazine.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Triflupromazine.
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Triflupromazine.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Triflupromazine.
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Triflupromazine.
GalantamineGalantamine may increase the central neurotoxic activities of Triflupromazine.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Triflupromazine.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Triflupromazine.
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Triflupromazine.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Triflupromazine.
LisdexamfetamineTriflupromazine may decrease the stimulatory activities of Lisdexamfetamine.
LithiumLithium may increase the neurotoxic activities of Triflupromazine.
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Triflupromazine.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Triflupromazine.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Triflupromazine.
MethamphetamineTriflupromazine may decrease the stimulatory activities of Methamphetamine.
MethylphenidateThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Triflupromazine.
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Triflupromazine.
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Triflupromazine.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Triflupromazine.
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Triflupromazine.
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Triflupromazine.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Triflupromazine.
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Triflupromazine.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Triflupromazine.
PhendimetrazineTriflupromazine may decrease the stimulatory activities of Phendimetrazine.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Triflupromazine.
PhentermineTriflupromazine may decrease the stimulatory activities of Phentermine.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Triflupromazine.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Triflupromazine.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Triflupromazine.
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Triflupromazine.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Triflupromazine.
RivastigmineRivastigmine may increase the central neurotoxic activities of Triflupromazine.
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Triflupromazine.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Triflupromazine.
SertralineThe risk or severity of adverse effects can be increased when Sertraline is combined with Triflupromazine.
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Triflupromazine.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Triflupromazine.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Triflupromazine.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Triflupromazine.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Triflupromazine.
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Triflupromazine.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Triflupromazine.
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Triflupromazine.
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Triflupromazine.
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Triflupromazine.
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Triflupromazine.
Food InteractionsNot Available

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
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
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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins ...
Gene Name:
HTR2B
Uniprot ID:
P41595
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
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
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
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11