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 serious 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 two-ringed tricyclic nucleus of benzene (“pheno”). The two rings are linked by a ring with a sulphur 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.


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

This led them to the discovery of promethazine and chlorpromazine, the former 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 shall see later).

Originally, phenothiazine 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.

Over time, phenothiazines became important beyond the textile dye industry. Based on various findings with phenothiazines and other dyes, they ended up having great repercussions in the drug industry.


Phenothiazines, in addition to being part of a group of antipsychotic drugs (because of their structure), are general purpose antiemetics (they prevent vomiting or nausea). They are effective in a wide variety of low or moderate intensity stimuli; in contrast, they are not effective in vomiting by potent emetics (stimuli that cause 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 great revolution for psychiatry and to start treating mental disorders from another perspective. Furthermore, it was the seed to start developing research in a field like psychopharmacology.

Like other phenothiazine antipsychotics, the effects (mechanism of action) of chlorpromazine are sedatives, antipsychotics, antiemetics and tranquilizers.


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

Side effects

Phenothiazines can produce various adverse effects, such as

Cholestatic jaundice

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

2. Blood dyscrasias

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

Agranulocytosis is the most serious , since it can cause death from 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 hives, or photosensitization . The administration of phenothiazines at high doses can also cause the appearance of areas of blue-greyish colouring in the areas of the body exposed to sunlight; on the other hand, with thioridazine, cases of retinopathy of pigmentation have been described.

Retinopathy of 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 initial stages, night and peripheral vision and leads to blindness.

Bibliographic references:

  • Krupp, P. and Barnes, P. (1989). Leponex-assocciated granulocytopenia: a review of the situation. Psychopharmacology, 99(Supl): S118-S121.
  • Pita, E. and Manzanares, J. (1992). Antipsychotic drugs. Neuropsychiatric Specialist Association, 12 (Suppl. 1).
  • Mazana, J.S., Pereira, J. and Cabrera, R. (2002). Fifty years of chlorpromazine. Rev Esp Sanid Penit; 4: 101-113.