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targets (3)
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Identification
Name Thiethylperazine
Accession Number DB00372 (APRD00323)
Type small molecule
Groups approved
Description

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)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Ethylthioperazine
Theithylperazine
Salts Not Available
Brand names
Name Company
Norzine
Torecan
Brand mixtures Not Available
Categories
  • Antiemetics
  • Dopamine Antagonists
  • Anti-emetics
CAS number 1420-55-9
Weight Average: 399.616
Monoisotopic: 399.180289323
Chemical Formula C22H29N3S2
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenothiazines
Substructures
  • Ethers
  • Phenothiazines
  • Aliphatic and Aryl Amines
  • Piperazines
  • Thiazines
  • Benzene and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication For the treatment or relief of nausea and vomiting.
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.
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
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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Solution Intramuscular
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
melting point 62-64 °C PhysProp
boiling point 227 °C at 1.00E-02 mm Hg PhysProp
water solubility 0.0584 mg/L Not Available
logP 5.41 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 4.87e-03 g/l ALOGPS
logP 5.12 ALOGPS
logP 4.66 ChemAxon
logS -4.9 ALOGPS
pKa (strongest basic) 8.4 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 9.72 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 122.56 ChemAxon
polarizability 46.53 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Maurer H, Pfleger K: Identification of phenothiazine antihistamines and their metabolites in urine. Arch Toxicol. 1988;62(2-3):185-91. Pubmed
External Links
Resource Link
KEGG Drug D02354 Link_out
KEGG Compound C07132 Link_out
PubChem Compound 5440 Link_out
PubChem Substance 46506502 Link_out
ChemSpider 5245 Link_out
ChEBI 9544 Link_out
ChEMBL 9544 Link_out
Therapeutic Targets Database DAP000315 Link_out
PharmGKB PA164748882 Link_out
RxList http://www.rxlist.com/cgi/generic2/thiethyl.htm Link_out
Drugs.com http://www.drugs.com/mtm/thiethylperazine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Thiethylperazine Link_out
ATC Codes
  • R06AD03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Bromocriptine The phenothiazine decreases the effect of bromocriptine
Cisapride Increased risk of cardiotoxicity and arrhythmias
Dexfenfluramine Decreased anorexic effect, may increase psychotic symptoms
Diethylpropion Decreased anorexic effect, may increase psychotic symptoms
Fenfluramine Decreased anorexic effect, may increase psychotic symptoms
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine Thiethylperazine may decrease the effect of guanethidine.
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Mazindol Decreased anorexic effect, may increase psychotic symptoms
Phentermine Decreased anorexic effect, may increase psychotic symptoms
Phenylpropanolamine Decreased anorexic effect, may increase psychotic symptoms
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Food Interactions Not Available
Targets

1. D(2) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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

2. D(1A) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

3. D(4) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out
Gene: DRD4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19