Identification

Summary

Thiethylperazine is a drug used for the treatment of nausea and vomiting.

Generic Name
Thiethylperazine
DrugBank Accession Number
DB00372
Background

A dopamine antagonist that is particularly useful in treating the nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness. (From AMA Drug Evaluations Annual, 1994, p457)

Type
Small Molecule
Groups
Approved, Withdrawn
Structure
Thumb
Weight
Average: 399.616
Monoisotopic: 399.180289323
Chemical Formula
C22H29N3S2
Synonyms
  • 2-(ethylthio)-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine
  • Norzine
  • Thiethylperazin
  • Thiéthylpérazine
  • Thiethylperazine
  • Thiethylperazinum
  • Tietilperazina
External IDs
  • GS 95
  • NSC 130044

Pharmacology

Indication

For the treatment or relief of nausea and vomiting.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Thiethylperazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, Thiethylperazine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.

Mechanism of action

Thiethylperazine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Thiethylperazine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with thiethylperazine.

TargetActionsOrganism
UDopamine D2 receptor
antagonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

60%

Metabolism
Not Available
Route of elimination

Thiethylperazine is eliminated in the urine.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Manifestations of acute overdosage of TORECAN (thiethylperazine) can be expected to reflect the CNS effects of the drug and include extrapyramidal symptoms (E.P.S), confusion and convulsions with reduced or absent reflexes, respiratory depression and hypotension.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with 1,2-Benzodiazepine.
AbacavirThiethylperazine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Thiethylperazine.
AceclofenacAceclofenac may decrease the excretion rate of Thiethylperazine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Thiethylperazine which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Thiethylperazine which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Acetazolamide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Thiethylperazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Acetophenazine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Thiethylperazine which could result in a higher serum level.
Interactions
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Food Interactions
  • Avoid excessive or chronic alcohol consumption. Additive CNS depression may occur if alcohol is consumed with thiethylperazine.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Thiethylperazine malateHP46XK89XB52239-63-1GTHHLZDYRHLACN-UHFFFAOYSA-N
Thiethylperazine maleateRUK64CF26E1179-69-7RVBRTNPNFYFDMZ-SPIKMXEPSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TorecanInjection, solution10 mg/2mLIntramuscularUNSPECIFIED2006-05-112006-10-13US flag
TorecanTablet10 mg/1OralUNSPECIFIED2006-05-112006-10-13US flag

Categories

ATC Codes
R06AD03 — Thiethylperazine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / Thiophenol ethers / N-methylpiperazines / Alkylarylthioethers / 1,4-thiazines / Trialkylamines / Sulfenyl compounds / Azacyclic compounds / Organopnictogen compounds
show 1 more
Substituents
1,4-diazinane / Alkylarylthioether / Alkyldiarylamine / Amine / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Diarylthioether / Hydrocarbon derivative
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, N-methylpiperazine (CHEBI:9544)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
8ETK1WAF6R
CAS number
1420-55-9
InChI Key
XCTYLCDETUVOIP-UHFFFAOYSA-N
InChI
InChI=1S/C22H29N3S2/c1-3-26-18-9-10-22-20(17-18)25(19-7-4-5-8-21(19)27-22)12-6-11-24-15-13-23(2)14-16-24/h4-5,7-10,17H,3,6,11-16H2,1-2H3
IUPAC Name
2-(ethylsulfanyl)-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine
SMILES
CCSC1=CC2=C(SC3=CC=CC=C3N2CCCN2CCN(C)CC2)C=C1

References

General References
  1. Maurer H, Pfleger K: Identification of phenothiazine antihistamines and their metabolites in urine. Arch Toxicol. 1988;62(2-3):185-91. [Article]
Human Metabolome Database
HMDB0014516
KEGG Drug
D02354
KEGG Compound
C07132
PubChem Compound
5440
PubChem Substance
46506502
ChemSpider
5245
BindingDB
78436
RxNav
10471
ChEBI
9544
ChEMBL
CHEMBL1378
ZINC
ZINC000022446674
Therapeutic Targets Database
DAP000315
PharmGKB
PA164748882
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Thiethylperazine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentAlzheimer's Disease (AD)1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Novartis AG
Dosage Forms
FormRouteStrength
Injection, solutionIntramuscular10 mg/2mL
PillOral6.5 mg
SuppositoryRectal6.5 MG
TabletOral10 mg/1
Tablet, coatedOral6.5 MG
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)62-64 °CPhysProp
boiling point (°C)227 °C at 1.00E-02 mm HgPhysProp
water solubility0.0584 mg/LNot Available
logP5.41HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00487 mg/mLALOGPS
logP5.12ALOGPS
logP4.66ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)8.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.72 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity122.56 m3·mol-1ChemAxon
Polarizability46.53 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9558
Blood Brain Barrier+0.9847
Caco-2 permeable+0.748
P-glycoprotein substrateSubstrate0.8705
P-glycoprotein inhibitor IInhibitor0.8683
P-glycoprotein inhibitor IIInhibitor0.6434
Renal organic cation transporterInhibitor0.715
CYP450 2C9 substrateNon-substrate0.8381
CYP450 2D6 substrateSubstrate0.7491
CYP450 3A4 substrateNon-substrate0.607
CYP450 1A2 substrateInhibitor0.9159
CYP450 2C9 inhibitorNon-inhibitor0.8968
CYP450 2D6 inhibitorInhibitor0.943
CYP450 2C19 inhibitorNon-inhibitor0.5565
CYP450 3A4 inhibitorNon-inhibitor0.7657
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.684
Ames testNon AMES toxic0.885
CarcinogenicityNon-carcinogens0.9366
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5624 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9258
hERG inhibition (predictor II)Inhibitor0.8292
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0000900000-66239882c220302aee87
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0400900000-67c33b4bb0599ec5f25e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01ox-1920000000-8306550db4ba65e81586
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03kc-6960000000-91d197f5c5cc7ac38c4d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0229-9560000000-c669a4875fb62a347fb8

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [Article]
  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. [Article]
  3. Briani C, Cagnin A, Chierichetti F, Tiberio M, Battistin L, Pizzolato G: Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2 receptors blockade. Eur J Neurol. 2004 Oct;11(10):709-10. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 17, 2021 04:16