Phenothiazines: characteristics and uses of this group of drugs

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 know the phenothiazines.

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

• Related article: "Types of psychoactive drugs: uses and side effects"

Phenothiazines: chemical compound

The term phenothiazines refers to chemical compounds containing a tricyclic nucleus of two benzene rings ("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 toxic to the environment.

Origin

Phenothiazines were initially used as antimalarials by Paul Ehrlich and later as antihistamines by Daniel Bovet. For their part, 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, this being the first substance recognized by Jean Delay and Pierre Deniker, which showed effective antipsychotic properties in the treatment of schizophrenia (the first antipsychotic, as we will see later). forward).

Originally, phenothiazine It was developed as a synthetic dye in the year 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.

With the passage of time, phenothiazines gained importance beyond the dyestuff industry to the textile industries. From various findings with phenothiazines and other dyes, these ended up having great repercussions in the drug industry.

Characteristics

phenothiazines, In addition to being part of a group of antipsychotic drugs (due to their structure), they are antiemetics for general use. (prevent vomiting or nausea). They are effective in a great variety of stimuli of low or moderate intensity; on the contrary, they are not effective in vomiting due to powerful emetics (stimuli that cause vomiting), such as chemotherapy with cisplatin.

It seems that there is a dose/effect relationship, but the occurrence of side effects limits the maximum dose. These effects include dystonic reactions (particularly in children), sedation, and hypotension.

• You may be interested in: "Types of antipsychotics (or neuroleptics)"

Chlorpromazine: the first antipsychotic

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

It was a great revolution for 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.

Guys

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

Side effects

Phenothiazines can cause various adverse effects, such as:

1. cholestatic jaundice

It is an adverse reaction of an allergic nature, associated with the use of phenothiazines. Its course is benign, reversing when stopping treatment or changing drugs. Its prevalence is estimated at 0.5% of treated subjects and it normally 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 mild leukocytosis, eosinophilia, or leukopenia.

Agranulocytosis is the most serious, since it can cause 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

Is about immediate hypersensitivity reactions, such as hives, or photosensitization. Administration of high doses of phenothiazines can also cause blue-gray areas to appear on 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 that affect the eye and are characterized by a slow and progressive loss of vision. Such loss affects, at least in its early stages, night and peripheral vision, and leads to blindness.