Phenothiazines: characteristics and uses of this group of drugs.

A group of drugs that began to be used in the textile industry and then moved on to medicine.

There are many types of antipsychotics, depending on their chemical structure, their discovery (first or second generation), their mechanism of action, etc. In this article we will learn about phenothiazines.

Phenothiazines form the chemical structure of a group of antipsychotic drugs, used to treat various severe mental and emotional disorders, as well as to reduce nausea and vomiting (antiemetic drug). Some phenothiazine drugs are Chlorpromazine and Levopromazine.

Phenothiazines: chemical compound

The term phenothiazines refers to chemical compounds containing a tricyclic nucleus of two benzene rings ("pheno"). ("pheno"). The two rings are linked through a ring with a sulfur atom ("thio") and a nitrogen atom ("azo"). A three-carbon side chain (aliphatic or cyclic) is attached to the nitrogen atom.

It is a yellowish or greenish crystalline compound, soluble in hot acetic acid, benzene and other solvents. Chemically it is a volatile organic compound and environmentally toxic.

Origin

Phenothiazines were initially used as antimalarials by Paul Ehrlich and later as antihistamines by Daniel Bovet. In turn, Henry Laborit and Pierre Huguenard used phenothiazines in anesthesia to counteract the effects of surgical shock..

This led them to the discovery of promethazine and chlorpromazine, the latter being the first substance, recognized by Jean Delay and Pierre Deniker, to show effective antipsychotic properties in the treatment of schizophrenia (the first antipsychotic, as we will see below).

Originally, phenothiazine was developed as a synthetic dye in 1883.. Its synthesis is due to the German organic chemist Bernthsen, at the end of the 19th century, during the development of dyes in the textile industry.

As time went by, phenothiazines gained importance beyond the dye industry for the textile industries. From various findings with phenothiazines and other dyes, these eventually had a major impact on the drug industry.

Characteristics

Phenothiazines, besides being part of a group of antipsychotic drugs (due to their structure), are antiemetics of general use (they prevent vomiting or nausea). (they prevent vomiting or nausea). They are effective in a wide variety of stimuli of low or moderate intensity; in contrast, they are not effective in vomiting by potent emetics (stimuli that provoke vomiting), such as cisplatin chemotherapy.

There seems to be a dose/effect relationship, but the occurrence of side effects limits the maximum dose. These effects consist of dystonic reactions (especially in children), sedation and hypotension.

Chlorpromazine: the first antipsychotic.

One of the best known phenothiazines is chlorpromazine. Chlorpromazine was the first phenothiazine antipsychotic available in pharmacotherapy (also the first, in general), and was discovered half a century ago.

It was a major revolution in psychiatry. and to start treating mental disorders from another perspective. In addition, it was the seed to start developing research in a field such as psychopharmacology.

Like other phenothiazine antipsychotics, the effects (mechanism of action) of chlorpromazine are sedative, antipsychotic, antiemetic and tranquilizing.

Types

There are three types of phenothiazinesaccording to their structure: aliphatic phenothiazines, with drugs such as Chlorpromazine and Levopromazine; piperidine phenothiazines (Thioridazine) and piperazine phenothiazines (Fluphenazine, Perphenazine and Trifluperazine).

Side effects

Phenothiazines can produce several adverse effects, such as:

1. cholestatic jaundice.

This is an adverse reaction of allergic nature, associated with the use of phenothiazines. Its course is benign, reversing when the treatment is suspended or when the drug is changed.. Its prevalence is estimated at 0.5% of treated subjects and usually appears in the first month of treatment.

2. Blood dyscrasias

This symptom is also allergic based. A blood dyscrasia is a blood disorder in any of the blood constituents. The most common dyscrasias are discrete leukocytosis, eosinophilia or leukopenia.

Agranulocytosis is the most severeIt can lead to death due to an immunodeficiency syndrome produced by the use of phenothiazines, especially clozapine. In the latter case, its prevalence is 10/1,000 treated subjects.

3. Dermatological reactions

These are immediate hypersensitivity reactions, such as urticaria, or photosensitization.. The administration of phenothiazines at high doses can also cause the appearance of areas of blue-gray coloration in areas of the body exposed to sunlight; on the other hand, cases of pigmentary retinopathy have been described with thioridazine.

Retinopathy pigmentosa or retinitis pigmentosa is a group of degenerative and hereditary diseases affecting the eye characterized by a slow and progressive loss of vision. This loss affects, at least in its early stages, night and peripheral vision and leads to blindness.