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Identification
NameThiethylperazine
Accession NumberDB00372  (APRD00323)
TypeSmall Molecule
GroupsWithdrawn
DescriptionA 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)
Structure
Thumb
Synonyms
2-(ethylthio)-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine
Norzine
Thiethylperazin
Thiéthylpérazine
Thiethylperazine
Thiethylperazinum
Tietilperazina
External Identifiers
  • GS 95
  • NSC 130044
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TorecanKrka
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Thiethylperazine malate
ThumbNot applicableDBSALT001328
Thiethylperazine maleate
ThumbNot applicableDBSALT001059
Categories
UNII8ETK1WAF6R
CAS number1420-55-9
WeightAverage: 399.616
Monoisotopic: 399.180289323
Chemical FormulaC22H29N3S2
InChI KeyInChIKey=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
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
  • Alkylarylthioether
  • N-alkylpiperazine
  • N-methylpiperazine
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Para-thiazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Sulfenyl compound
  • Thioether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment or relief of nausea and vomiting.
PharmacodynamicsThiethylperazine, 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 actionThiethylperazine 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding60%
MetabolismNot Available
Route of eliminationThiethylperazine is eliminated in the urine.
Half lifeNot Available
ClearanceNot Available
ToxicityManifestations 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.
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+0.9558
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point62-64 °CPhysProp
boiling point227 °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
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Maurer H, Pfleger K: Identification of phenothiazine antihistamines and their metabolites in urine. Arch Toxicol. 1988;62(2-3):185-91. [PubMed:2904251 ]
External Links
ATC CodesR06AD03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
5'-Deoxy-5'-MethylthioadenosineThe serum concentration of Thiethylperazine can be increased when it is combined with 5'-Deoxy-5'-Methylthioadenosine.
AcebutololThiethylperazine may increase the hypotensive activities of Acebutolol.
AlfentanilThiethylperazine may increase the hypotensive activities of Alfentanil.
AlphacetylmethadolThiethylperazine may increase the hypotensive activities of Alphacetylmethadol.
AlprenololThiethylperazine may increase the hypotensive activities of Alprenolol.
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum phosphateAluminum phosphate can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmodiaquineThe serum concentration of Thiethylperazine can be increased when it is combined with Amodiaquine.
AmoxapineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Amoxapine.
ArotinololThiethylperazine may increase the hypotensive activities of Arotinolol.
ArtemetherThe serum concentration of Thiethylperazine can be increased when it is combined with Artemether.
ArtesunateThe serum concentration of Thiethylperazine can be increased when it is combined with Artesunate.
AtenololThiethylperazine may increase the hypotensive activities of Atenolol.
AtovaquoneThe serum concentration of Thiethylperazine can be increased when it is combined with Atovaquone.
BefunololThiethylperazine may increase the hypotensive activities of Befunolol.
BetaxololThiethylperazine may increase the hypotensive activities of Betaxolol.
BevantololThiethylperazine may increase the hypotensive activities of Bevantolol.
BezitramideThiethylperazine may increase the hypotensive activities of Bezitramide.
Bismuth SubcitrateBismuth Subcitrate can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
BisoprololThiethylperazine may increase the hypotensive activities of Bisoprolol.
BopindololThiethylperazine may increase the hypotensive activities of Bopindolol.
BufuralolThiethylperazine may increase the hypotensive activities of Bufuralol.
BupranololThiethylperazine may increase the hypotensive activities of Bupranolol.
BuprenorphineThiethylperazine may increase the hypotensive activities of Buprenorphine.
ButorphanolThiethylperazine may increase the hypotensive activities of Butorphanol.
Calcium carbonateCalcium carbonate can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
CarfentanilThiethylperazine may increase the hypotensive activities of Carfentanil.
CarteololThiethylperazine may increase the hypotensive activities of Carteolol.
CarvedilolThiethylperazine may increase the hypotensive activities of Carvedilol.
CeliprololThiethylperazine may increase the hypotensive activities of Celiprolol.
ChloroquineThe serum concentration of Thiethylperazine can be increased when it is combined with Chloroquine.
CitalopramThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Citalopram.
ClomipramineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Clomipramine.
CodeineThiethylperazine may increase the hypotensive activities of Codeine.
DapoxetineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Dapoxetine.
DapsoneThe serum concentration of Thiethylperazine can be increased when it is combined with Dapsone.
DextromoramideThiethylperazine may increase the hypotensive activities of Dextromoramide.
DextropropoxypheneThiethylperazine may increase the hypotensive activities of Dextropropoxyphene.
DezocineThiethylperazine may increase the hypotensive activities of Dezocine.
DihydrocodeineThiethylperazine may increase the hypotensive activities of Dihydrocodeine.
DihydroetorphineThiethylperazine may increase the hypotensive activities of Dihydroetorphine.
DihydromorphineThiethylperazine may increase the hypotensive activities of Dihydromorphine.
DiphenoxylateThiethylperazine may increase the hypotensive activities of Diphenoxylate.
DoxycyclineThe serum concentration of Thiethylperazine can be increased when it is combined with Doxycycline.
DPDPEThiethylperazine may increase the hypotensive activities of DPDPE.
EscitalopramThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Escitalopram.
EsmololThiethylperazine may increase the hypotensive activities of Esmolol.
EthylmorphineThiethylperazine may increase the hypotensive activities of Ethylmorphine.
EtoperidoneThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Etoperidone.
EtorphineThiethylperazine may increase the hypotensive activities of Etorphine.
FenfluramineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Fenfluramine.
FentanylThiethylperazine may increase the hypotensive activities of Fentanyl.
FluoxetineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Fluoxetine.
FluvoxamineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Fluvoxamine.
HalofantrineThe serum concentration of Thiethylperazine can be increased when it is combined with Halofantrine.
HeroinThiethylperazine may increase the hypotensive activities of Heroin.
HydrocodoneThiethylperazine may increase the hypotensive activities of Hydrocodone.
HydromorphoneThiethylperazine may increase the hypotensive activities of Hydromorphone.
HydroxychloroquineThe serum concentration of Thiethylperazine can be increased when it is combined with Hydroxychloroquine.
IndalpineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Indalpine.
IndenololThiethylperazine may increase the hypotensive activities of Indenolol.
KetobemidoneThiethylperazine may increase the hypotensive activities of Ketobemidone.
LabetalolThiethylperazine may increase the hypotensive activities of Labetalol.
LevobunololThiethylperazine may increase the hypotensive activities of Levobunolol.
Levomethadyl AcetateThiethylperazine may increase the hypotensive activities of Levomethadyl Acetate.
LevomilnacipranThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Levomilnacipran.
LevorphanolThiethylperazine may increase the hypotensive activities of Levorphanol.
LofentanilThiethylperazine may increase the hypotensive activities of Lofentanil.
Lu AA21004The risk or severity of adverse effects can be increased when Thiethylperazine is combined with Lu AA21004.
LumefantrineThe serum concentration of Thiethylperazine can be increased when it is combined with Lumefantrine.
MagaldrateMagaldrate can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium carbonateMagnesium carbonate can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium hydroxideMagnesium hydroxide can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium oxideMagnesium oxide can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium TrisilicateMagnesium Trisilicate can cause a decrease in the absorption of Thiethylperazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
MefloquineThe serum concentration of Thiethylperazine can be increased when it is combined with Mefloquine.
MethadoneThiethylperazine may increase the hypotensive activities of Methadone.
Methadyl AcetateThiethylperazine may increase the hypotensive activities of Methadyl Acetate.
MetipranololThiethylperazine may increase the hypotensive activities of Metipranolol.
MetoprololThiethylperazine may increase the hypotensive activities of Metoprolol.
MilnacipranThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Milnacipran.
MorphineThiethylperazine may increase the hypotensive activities of Morphine.
NadololThiethylperazine may increase the hypotensive activities of Nadolol.
NalbuphineThiethylperazine may increase the hypotensive activities of Nalbuphine.
NormethadoneThiethylperazine may increase the hypotensive activities of Normethadone.
OlanzapineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Olanzapine.
OpiumThiethylperazine may increase the hypotensive activities of Opium.
OxprenololThiethylperazine may increase the hypotensive activities of Oxprenolol.
OxycodoneThiethylperazine may increase the hypotensive activities of Oxycodone.
OxymorphoneThiethylperazine may increase the hypotensive activities of Oxymorphone.
ParoxetineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Paroxetine.
PenbutololThiethylperazine may increase the hypotensive activities of Penbutolol.
PentazocineThiethylperazine may increase the hypotensive activities of Pentazocine.
PethidineThiethylperazine may increase the hypotensive activities of Pethidine.
PindololThiethylperazine may increase the hypotensive activities of Pindolol.
PractololThiethylperazine may increase the hypotensive activities of Practolol.
PrimaquineThe serum concentration of Thiethylperazine can be increased when it is combined with Primaquine.
ProguanilThe serum concentration of Thiethylperazine can be increased when it is combined with Proguanil.
PropranololThiethylperazine may increase the hypotensive activities of Propranolol.
PyrimethamineThe serum concentration of Thiethylperazine can be increased when it is combined with Pyrimethamine.
QuinacrineThe serum concentration of Thiethylperazine can be increased when it is combined with Quinacrine.
QuinidineThe serum concentration of Thiethylperazine can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Thiethylperazine can be increased when it is combined with Quinine.
RadicicolThe serum concentration of Thiethylperazine can be increased when it is combined with Radicicol.
RemifentanilThiethylperazine may increase the hypotensive activities of Remifentanil.
SertralineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Sertraline.
SinefunginThe serum concentration of Thiethylperazine can be increased when it is combined with Sinefungin.
SotalolThiethylperazine may increase the hypotensive activities of Sotalol.
SufentanilThiethylperazine may increase the hypotensive activities of Sufentanil.
SulfadoxineThe serum concentration of Thiethylperazine can be increased when it is combined with Sulfadoxine.
SulfametopyrazineThe serum concentration of Thiethylperazine can be increased when it is combined with Sulfametopyrazine.
tafenoquineThe serum concentration of Thiethylperazine can be increased when it is combined with tafenoquine.
TapentadolThiethylperazine may increase the hypotensive activities of Tapentadol.
ThiopentalThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Thiopental.
TimololThiethylperazine may increase the hypotensive activities of Timolol.
TramadolThiethylperazine may increase the hypotensive activities of Tramadol.
TrazodoneThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Trazodone.
TrimethoprimThe serum concentration of Thiethylperazine can be increased when it is combined with Trimethoprim.
VilazodoneThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Vilazodone.
VortioxetineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Vortioxetine.
ZimelidineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Zimelidine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
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 ]
  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. [PubMed:15469457 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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
unknown
Actions
antagonist
General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23