Thiethylperazine

Thiethylperazine activates the transport protein ABCC1 that clears beta-amyloid from brains of mice.

Pharmacokinetics

Distribution

Thiethylperazine 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 metabolized in the liver and only 3% is eliminated unchanged. Thiethylperazine's half-life is 12 h.

Teratogenicity

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

Antipsychotic activity

Theithylperazine may possess antipsychotic activity due to the antagonism of 5-HT2 and D2 receptors. It can cause extrapyramidal symptoms. Nevertheless, it was never marketed as an antipsychotic.

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.

Synthesis

One synthesis of thiethylperazine begins with a Goldberg reaction between 3-(ethylsulfanyl)aniline (1) and 2-chlorobenzoic acid (2) to give the diarylamine 3. The carboxyl in the anthranilic acid residue, having performed its activating function, is then thermolytically removed to form (4). Upon treatment with sulfur and iodine, we get predominantly the phenothiazine (5). The reaction may well be aided by the presence of the electron donating thioether at the para-position. Alkylation with 1-(γ-chloropropyl)-4-methylpiperazine (6) in the presence of sodamide affords thiethylperazine (7).

References

References

1. (February 1965). "The Effects of Thiethylperazine Dimaleate (Torecan) on Nausea and Vomiting". Canadian Medical Association Journal.
2. "Charakterystyka Produktu Leczniczego".
3. (September 1978). "Thiethylperazine; clinical antipsychotic efficacy and correlation with potency in predictive systems". Archives of General Psychiatry.
4. (July 1985). "Recurrent dystonic reactions induced by thiethylperazine". Drug Intelligence & Clinical Pharmacy.
5. (1958). "Synthesen auf dem Phenothiazin-Gebiet. 1. Mitteilung. Mercaptophenothiazin-Derivate.". Helvetica Chimica Acta.
6. (1958). "Synthesen auf dem Phenothiazin-Gebiet. 2. Mitteilung. N-substituierte Mercaptophenothiazin-Derivate.". Helvetica Chimica Acta.
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