thiethylperazine

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.

Originator

Torecan,Boehringer Ingelheim,US,1961

The Uses of thiethylperazine

Thiethylperazine acts both as a peripheral and as a central antiemetic.

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)

Indications

For the treatment or relief of nausea and vomiting.

Definition

ChEBI: A member of the class of phenothiazines that is perazine substituted by a ethylsulfanyl group at position 2.

Manufacturing Process

26.1 parts of 3-ethylmercapto-phenothiazine (melting point 95°C to 97°C), 4.7 parts of finely pulverized sodium amide and 120 parts by volume of absolute xylene are heated to boiling for two hours, under reflux and while stirring the reaction mixture, at an oil-bath temperature of 180°C. Without interrupting the heating, a solution of 20.0 parts of 1-methyl-4-(3'- chloropropyl-1')-piperazine (boiling point 95°C to 97°C at a pressure of 10 mm Hg) in 20 parts by volume of xylene is added dropwise in the course of 1 1/2 hours. After heating 3 more hours, the reaction mixture is cooled and 10.0 parts of ammonium chloride added; the mixture is then shaken out three times, using 50 parts by volume of water each time. The xylene solution is extracted with 250 parts by volume of aqueous tartaric acid of 15% strength, after which the tartaric acid extract is washed with 80 parts by volume of benzene and then rendered phenolphthalein-alkaline by the addition of 60 parts by volume of concentrated aqueous caustic soda solution. The base which precipitates is taken up in a total of 150 parts by volume of benzene; the benzene layer is dried over potassium carbonate and is then evaporated under reduced pressure. The residue from the evaporation is distilled in a high vacuum. After separating a preliminary distillate which passes over up to 226°C under a pressure of 0.01 mm Hg the main fraction - 3-ethylmercapto- 10-[3'-(1''-methyl-piperazyl-4'')-propyl-1']-phenothiazine - which distills at 226°C to 228°C under the last-mentioned pressure is collected. The analytically pure base boils at 227°C under a pressure of 0.01 mm Hg and melts at 62°C to 64°C.
Upon the addition of ethanolic HCl to a solution, cooled to 0°C, of 26.38 parts of the free base in 130 parts by volume of absolute ethanol, until a Congoacid reaction is achieved, the crystalline dihydrochloride of 3-ethylmercapto- 10-[3'-(1''-methyl-piperazyl-4'')-propyl-1']phenothiazine is precipitated. The analytically pure salt has a melting point of 214°C to 216°C (bubbles); it begins to sinter at 205°C. The dimaleate melts at 188°C to 190°C after sintering from 180°C (recrystallized from methanol).

Therapeutic Function

Antiemetic

Trade name

Torecan (Boehringer Ingelheim)

Pharmacokinetics

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.

Metabolism

Not Available