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Thorazine - An Old Fashioned Cure-All

Thorazine was thought of as a revolutionary breakthrough medication similar to Penicillin when the FDA approved it's use in the early 1950's. It was the very first psychiatric medication useful in the treatment of schizophrenia. Before Thorazine, institutions used leather restraints, alternating cold and hot body packs and of course crude psychosurgery such as lobotomy...

Thorazine was discovered while searching for a cure for malaria and worked by blocking dopamine receptors in the brain - a chemical lobotomy. After Thorazine disables the dopamine receptors all sorts of bad things happen. Blocking dopamine does blunt the psychosis, but fooling around with neurotransmitters never has…

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 Back to the Future: Thorazine for Sanity

Things got better. They also got worse. Thorazine was called a chemical lobotomy. Phenothiazine medications work by creating a strong blockade of dopamine receptors in the brain. In the years that have elapsed since this compound was first synthesized, we've learned that the brain doesn't really like when the dopamine receptors are blocked. In the first weeks after the medication is introduced into a body, the brain responds by dramatically increasing the amount of dopamine pumped into the synaptic cleft. In response to this increase of dopamine, the brain also dramatically increases the number of dopamine receptors. The medications, however, are highly effective compounds. Despite there being more dopamine and more receptors to hear the message of that dopamine, nothing happens. After about three weeks of phenothiazine treatment, the dopamine system starts to break down.

Articles of Interest

Chlorpromazine for treating aggression or agitation due to psychosis

Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed.

Chlorpromazine in Delirium FTW!

Bottom line here: escalating haloperidol, rotating to chlorpromazine, or doing a little of both are equally helpful in getting terminally agitated patients more comfortable appearing at 24 h, but switching to chlorpromazine is probably the fastest method. So, pretty good study. To me, it's an argument that I should be rapidly switching to chlorpromazine when I think death is imminent (days) and a few doses of haloperidol have not achieved much.

Chlorpromazine in the Treatment of Psychosis

The pharmacokinetics of chlorpromazine is also not fully understood and varies per the individual and route of administration. However, the kidneys excrete approximately 43-65% of the daily dose within 24 hours. There are 5 clinically important metabolites, 4 of which are biologically active.

Chlorpromazine, the first antipsychotic medication: history, controversy and legacy

Chlorpromazine was synthesized in 1950 by the French pharmaceutical company Rhône-Poulenc, but was not originally planned to be a psychiatric drug. The company was developing antihistaminergic drugs for use in a range of conditions including nausea and allergies.

Chlorpromazine: The Story of Phenothiazine Derivatives, Their Clinical Indications,...

In the closing years of the Second World War, various phenothiazine derivatives were examined independently in the United States and in France. The hoped for anti-malarial properties of these phenothiazine derivatives, however, did not materialize and the study of these chemicals was discontinued in America. In France, the remarkable anti-histaminic properties of some of these compounds were discovered, in particular, of the compound promethazine (Phenergan). Later the vagolytic properties of diethazine (Diparcol) were discovered and its excellent effect in the treatment of Parkinsonism.

Fifty years chlorpromazine: a historical perspective

Chlorpromazine was synthesized in December 1951 in the laboratories of Rhône-Poiulenc, and became available on prescription in France in November 1952. Its effectiveness was reflected in the transformation of disturbed wards; its commercial success stimulated the development of other psychotropic drugs. Recognition of chemical mediation at the site of the synapse, followed by the introduction of the spectrophotofluorimeter first, and receptor assays subsequently, led to the demonstration that chlorpromazine blocks dopamine receptors.

History of the discovery and clinical introduction of chlorpromazine

The discovery of phenothiazines, the first family of antipsychotic agents has its origin in the development of German dye industry, at the end of the 19th century (Graebe, Liebermann, Bernthsen). Up to 1940 they were employed as antiseptics, antihelminthics and antimalarials (Ehrlich, Schulemann, Gilman).

What is Thorazine?

The brand name Thorazine has been discontinued in the United States, but the active ingredient in Thorazine, chlorpromazine, is available in a variety of generic formulations. We’ll use the name Thorazine in this article, as it’s commonly used in place of chlorpromazine, and better known by patients seeking mental health treatment.

“This is a very bad idea, Peter… seriously!”

My view is… this medication is contentious, but also extremely common. Very frequently, people have no choice about taking it.

Resources

Medworks Media

Chlorpromazine is indicated for use in the treatment of schizophrenia; to control nausea and vomiting; for relief of restlessness and apprehension before surgery; for acute intermittent porphyria; as an adjunct in the treatment of tetanus; to control the manifestations of the manic type of manic-depressive illness; for relief of intractable hiccups...