Thiethylperazine (Torecan, Norzine) is an

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They m ...

of the

phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...

class. It is an antagonist of

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

s (

DRD1 Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family - receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene. Tissue distribution D1 receptors are the most abundant kind of do ...

DRD2 Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, i ...

DRD4 The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the gene on chromosome 11 at 11p15.5. The structure of DRD4 was recently reported in complex with the antipsychotic drug nemonapride. As with other dopamine ...

) as well as of 5-HT_2A, 5-HT_2C receptors,

mAChRs Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

(1 through 5), α₁ adrenergic receptor and H₁ receptor. Thiethylperazine activates the transport protein

ABCC1 Multidrug resistance-associated protein 1 (MRP1) is a protein that in humans is encoded by the ''ABCC1'' gene. Function The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins t ...

that clears beta-amyloid from brains of mice. *

Pharmacokinetics

Distribution

This drug is highly lipofilic and it binds with membranes and serum proteins (over 85%). It accumulates in organs with high blood flow and penetrates the placenta. It cannot be removed with dialysis.

Metabolism

It is mainly metabolised in the liver and only 3% is eliminated unchanged. Torecan's

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

is 12 h.

Teratogenicity

In toxic doses above the terapeutic window, it increases the rate of cleft palate occurrence.

Antypsychotic activity

Theithylperazine may possess antypsychotic activity due to the antagonism of 5-HT₂ and D₂ receptors. Because of this, it would not cause

extrapyramidal symptoms Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

. Nevertheless, it was never marketed as such drug. One cause of acute dystonia occurred in a 19-year-old male patient after discontinuation of this drug.

Overdose

Signs of acute thiethylperazine overdose include: extrapyramidal symptoms, confusion, convulsions, respiratory depression and

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

Synthesis

Goldberg reaction between 3-(ethylsulfanyl)aniline 783-82-0(1) and

2-chlorobenzoic acid 2-Chlorobenzoic acid is an organic compound with the formula ClC6H4CO2H. It is one of three isomeric chlorobenzoic acids, the one that is the strongest acid. This white solid is used as a precursor to a variety of drugs, food additives, and dye ...

18-91-2(2) to give the diarylamine
CID:82254530
(3). The carboxyl in the anthranilic acid

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

, having performed its activating function, is then thermolytically removed to form

8083-49-8 8 (eight) is the natural number following 7 and preceding 9. In mathematics 8 is: * a composite number, its proper divisors being , , and . It is twice 4 or four times 2. * a power of two, being 2 (two cubed), and is the first number of t ...

(4). Upon treatment with sulfur and iodine, we get predominantly the

6815-10-5(5); The rxn may well be aided by the presence of the electron donating

thioether In organic chemistry, an organic sulfide (British English sulphide) or thioether is an organosulfur functional group with the connectivity as shown on right. Like many other sulfur-containing compounds, volatile sulfides have foul odors. A su ...

at the ''para''-position. Alkylation with 1-(ɣ̞-chloropropyl)-4-methylpiperazine 04-16-5(6) in the presence of sodamide affords ''Thiethylperazine'' (7).

References

Antiemetics Piperazines Phenothiazines Thioethers {{nervous-system-drug-stub