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 (antiemetic drug). Some phenothiazine drugs are Chlorpromazine and Levopromazine.
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 and environmentally toxic organic compound.
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, that showed effective antipsychotic properties in the treatment of schizophrenia (the first antipsychotic, as we will see later).
Originally, phenothiazine It 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 textile industries. Based on various discoveries with phenothiazines and other dyes, these ended up having great repercussions on the drug industry.
Characteristics
Phenothiazines, In addition to being part of a group of antipsychotic drugs (due to their structure), they are generally used antiemetics (prevents vomiting or nausea). They are effective on a wide variety of low or moderate intensity stimuli; On the other hand, they are not effective in vomiting due to powerful emetics (stimuli that cause vomiting), such as chemotherapy with cisplatin.
There appears to be a dose/effect relationship, but the appearance 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 represented a great revolution for psychiatry and to start treating mental disorders from another perspective. Furthermore, it was the seed to begin 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; piperidine phenothiazines (Thioridazine) and piperazine phenothiazines (Fluphenazine, Perphenazine and Trifluperazine).
Side effects
Phenothiazines can produce various adverse effects, such as:
1. Cholestatic jaundice
This 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 normally appears in the first month of treatment.
This symptom is also allergic based. A blood dyscrasia is a blood disorder in any of the constituents of the blood. The most common dyscrasias are discrete leukocytosis, eosinophilia or leukopenia.
Agranulocytosis is the most serious, since it can cause death due to an immunodeficiency syndrome caused 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 urticaria, or photosensitization Administration of phenothiazines at high doses can also cause the appearance of blue-gray areas 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 that affect the eye and are characterized by a slow and progressive loss of vision. This loss affects, at least in its initial stages, night and peripheral vision, and leads to blindness.
