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Trifluoperazine Hydrochloride

HCID 66064
NotesReactions
Basic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
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Basic information

CAS
440-17-5
Standard SMILES
CN1CCN(CCCN2c3ccccc3Sc3ccc(C(F)(F)F)cc32)CC1.Cl.Cl
InChIKey
BXDAOUXDMHXPDI-UHFFFAOYSA-N
Molecular formula
C21H26Cl2F3N3S
Average molar mass
480.4 g/mol
Monoisotopic mass
479.1176589

Overview

Trifluoperazine Hydrochloride is the hydrochloride salt of trifluoperazine, a phenothiazine derivative and a dopamine, alpha-adrenergic, and anticholinergic antagonist with antipsychotic, anxiolytic, and antiemetic activities. Trifluoperazine blocks central dopamine receptors, which may prevent or mitigate delusions and hallucinations caused by an excess of dopamine; dopamine blockade in the chemoreceptor trigger zone (CTZ) may result in an antiemetic effect. This agent binds to central adrenergic receptors, which may result in anxiolytic effects. Trifluoperazine also functions as a calmodulin inhibitor, elevating cytosolic calcium.

Names & identifiers

Preferred name
Trifluoperazine Hydrochloride
IUPAC
10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)phenothiazine;dihydrochloride
English name
Trifluoperazine dihydrochloride
Molecular formula
C21H26Cl2F3N3S
Molecular weight
480.42

Names & synonyms

Trifluoperazine dihydrochloride440-17-5Trifluoperazine hydrochlorideTrifluoperazine HClEskazineTrifluoroperazine dihydrochlorideDTXSID1045085SKF 5019Trifluperazine dihydrochloride6P1Y2SNF5V10-(3-(4-methylpiperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine dihydrochloride10-[3-(4-Methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10H-phenothiazine dihydrochloride
Show more names
Trifluoperazine dihydrochloride, 10-[3-(4-Methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10H-phenothiazine dihydrochlorideUrinoxskf5019StelazinSTELAZINEEskazinylAi3-50137
NSC-75736910H-Phenothiazine, 10-(3-(4-methyl-1-piperazinyl)propyl)-2-(trifluoromethyl)-, dihydrochlorideDTXCID902508510-(3-(4-Methyl-1-piperazinyl)propyl)-2-(trifluoromethyl)phenothiazine dihydrochloride2-Trifluoromethyl-10-(3'-(1-methyl-4-piperazinyl)propyl)phenothiazine dihydrochloride10H-phenothiazine, 10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)-, dihydrochlorideCHEBI:9710NSC17474

Properties

Computed structural properties

Topological polar surface area
35 Ų
Hydrogen bond donors
2
Hydrogen bond acceptors
7
Rotatable bonds
4
Heavy atoms
30
Formal charge
0
Complexity
510

Experimental & physicochemical properties

Human Drugs · 2 items

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Collision Cross Section188.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Physicochemical properties

Melting point
243 °C · 243 °C (dec.)(lit.)
Flash point
9 ℃ · 9℃
storage temp.
-20 °C · -20°C
solubility
5 mg/mL · ethanol: soluble5mg/mL
pka
1 · pK1 3.9, pK2 8.1(at 25℃)
form
powder
color
white to off-white
Water Solubility
50 g/L, · water: 50g/L, clear
λmax
312 nm · 312nm(MeOH)(lit.)
Merck
14 · 14,9680
BRN
3820024 · 3820024
Stability

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 4 items

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 42 reports by companies from 3 notifications to the ECHA C&L Inventory.

Hazard information

Regulatory InformationHazard Traits - Bioaccumulation; Environmental Persistence
Other Safety InformationIMAP assessments - 10H-Phenothiazine, 10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)-, dihydrochloride: Environment tier I assessment
Hazard Classes and CategoriesAcute Tox. 4 (100%)

Toxicology

Treatment · 1 item

Treatment is essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage. Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus. Extrapyramidal symptoms may be treated with anti-parkinsonism drugs, barbiturates or Benadryl. See prescribing information for these products. Care should be taken to avoid increasing respiratory depression. If administration of a stimulant is desirable, amphetamine, dextroamphetamine or caffeine with sodium benzoate is recommended. Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided. If hypotension occurs, the standard measures for managing circulatory shock should be initiated. If it is desirable to administer a vasoconstrictor, Levophed and Neo-Synephrine are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause a further lowering of blood pressure. (L1712)

Chemistry & industry

Pharmacology

Metabolism/MetabolitesHepatic. Half Life: 10-20 hours
FDA Pharmacological Classification · 2 items

TRIFLUOPERAZINE HYDROCHLORIDE

Phenothiazines [CS]; Phenothiazine [EPC]

MeSH Pharmacological Classification · 3 items

Drugs used to prevent NAUSEA or VOMITING.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Uses & manufacturing

UsesFor the treatment of anxiety disorders, depressive symptoms secondary to anxiety and agitation.
General Manufacturing Information10H-Phenothiazine, 10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)-, hydrochloride (1:2): ACTIVE
Applications · 4 items

Related reactions

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Compound notes

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On this pageBasic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes

Database identifiers

CAS
440-17-5
PubChem CID
66064
DTXSID
DTXSID1045085
ChEMBL
CHEMBL1257040
UNII
6P1Y2SNF5V
EC Number
207-123-0
Hygroscopic
InChI
1S/C21H24F3N3S.2ClH/c1-25-11-13-26(14-12-25)9-4-10-27-17-5-2-3-6-19(17)28-20-8-7-16(15-18(20)27)21(22,23)24;;/h2-3,5-8,15H,4,9-14H2,1H3;2*1H
InChIKey
BXDAOUXDMHXPDI-UHFFFAOYSA-N
SMILES
Cl[H].Cl[H].CN1CCN(CCCN2c3ccccc3Sc4ccc(cc24)C(F)(F)F)CC1
CAS DataBase Reference
440 · 440-17-5(CAS DataBase Reference)
FDA UNII
6 P1Y2SNF5V · 6P1Y2SNF5V
NCI Drug Dictionary
Stelazine
EPA Substance Registry System
10 H-Phenothiazine, · 10H-Phenothiazine, 10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)-, dihydrochloride (440-17-5)
UNSPSC Code
41116107 · 41116107
NACRES
77 · NA.77
Symbol(GHS)
7 · GHS07,GHS08,GHS09
Signal word
Danger
Hazard statements
302 · H302-H319-H336-H341-H372-H410
Precautionary statements
201 · P201-P273-P301+P312+P330-P305+P351+P338-P308+P313
target organs
Central nervous system, Eyes
PPE
95 · dust mask type N95 (US), Eyeshields, Gloves
Hazard Codes
Xn
Risk Statements
22 · 22
Safety Statements
36 · 36
RIDADR
1230 · UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany
3 · 3
RTECS
1750000 · SP1750000
F
3 · 3-10
TSCA
TSCA listed
HazardClass
9 · 9
HS Code
29343000 · 29343000
Storage Class
6.1 C · 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Hazard Classifications
4 OralAquatic · Acute Tox. 4 OralAquatic Acute 1Aquatic Chronic 1Eye Irrit. 2Muta. 2STOT RE 1STOT SE 3
Limited Quantities
5 kg · 5.0 kg (11 lbs) (solid)
Excepted Quantities
Max Inner Pack (30g or 30ml) and Max Outer Pack (1Kg or 1L)
Exposure RoutesOral
Toxicity Summary · 1 item

Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Signs and SymptomsSymptoms 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.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury · 6 items

Drug Induced Liver Injury Rank (DILIrank 2.0)

Trifluoperazine hydrochloride

vLess-DILI-concern

2

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

Safety data

F
3-10
PPE
dust mask type N95 (US), Eyeshields, Gloves
wgk
3
tsca
TSCA listed
rtecs
SP1750000
ridadr
UN1230 - class 3 - PG 2 - Methanol, solution
hs_code
29343000
risk_code
22
Signal word
Danger
Symbol(GHS)
GHS07,GHS08,GHS09
hazard_code
Xn
safety_code
36
hazard_class
9
Storage Class
6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
target organs
Central nervous system, Eyes
Hazard statements
H302-H319-H336-H341-H372-H410
Limited Quantities
5.0 kg (11 lbs) (solid)
Excepted Quantities
Max Inner Pack (30g or 30ml) and Max Outer Pack (1Kg or 1L)
Hazard Classifications
Acute Tox. 4 OralAquatic Acute 1Aquatic Chronic 1Eye Irrit. 2Muta. 2STOT RE 1STOT SE 3
Precautionary statements
P201-P273-P301+P312+P330-P305+P351+P338-P308+P313

DescriptionTrifluoperazine (TFP) is a phenothiazine compound with anti-adrenergic and anti-dopaminergic actions typical of antipsychotic agents. It antagonizes adrenergic receptors, with selectivity for α1 over the α2 subtypes (Kis = 24, 653, 163, and 391 nM for α1A, α2A, α2B, and α2C, respectively). TFP binds with much higher affinity to the dopamine D2-like receptor (Kd = 0.96 nM) compared to the dopamine D4-like and the serotonin 5-HT2A receptors (Kds = 44 and 135 nM, respectively). Furthermore, TFP antagonizes calmodulin (CaM) and alters the calcium-binding properties of calsequestrin (CSQ). TFP has been shown to activate type-2 ryanodine receptors independently of its CaM and CSQ activity.

UsesTrifluoperazine dihydrochloride has been used as a calmodulin kinase antagonist in cultured Aplysia californica neurons. Trifluoperazine dihydrochloride has also been used as a PMCA inhibitor in mouse duodenal tissues to block the transcellular active calcium flux.

UsesAntipsychotic

General DescriptionTrifluoperazinehydrochloride, 10-[3-(4-Methyl-1-piperazinyl)propyl-[2-(trifluoromethyl)phenothiazine dihydrochloride (Stelazine).The absorption of trifluoperazine is erratic and variable andit is widely distributed into tissues. The excretion of trifluoperazineoccurs 50% via kidneys and the other 50% isthrough enterohepatic circulation. The metabolism and druginteractions of trifluoperazine are the same as with the otherphenothiazines. Trifluoperazine does not show any specificdrug interactions. Trifluoperazine is indicated for the managementof schizophrenia and short-term treatment ofnonpsychotic anxiety.

Upstream & downstream products

Upstream raw materials

1-Methyl-4-(3-chloropropyl)piperazine2-(Trifluoromethyl)phenothiazineSodium amide

Downstream products

trifluoperazine sulfoxide

Suppliers100 total

国药集团化学试剂有限公司86-21-63210123 · [email protected]
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