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This post provides deep knowledge about the drug called Phenothiazine along with its synthesis, action mechanisms, uses and side effects.

Do you know? Phenothiazine is a class of drug that is used to treat mental disorders or psychotic disorders.

But there’s more. And this is what we are discussing in this post. We try to cover the uses, side effects, the process of synthesis and the mechanism of action of Phenothiazine on the human body.

Before jumping directly to all the above-mentioned topics let’s discuss in short what is a Phenothiazine drug.

What is Phenothiazine?

Phenothiazine is abbreviated as PTZ which is an organic drug that is derived from the thiazine class. In history, the derivatives of Phenothiazine drugs have revolutionized not only the field of psychiatry but also for allergic treatment.


While talking about Phenothiazine drugs, it is an antipsychotic drug that is used to treat schizophrenia-like diseases and mental disorders. But some drugs are employed to treat other diseases and conditions like nausea, vomiting, and hiccups.

Hence, it is a type of drug that facilitates antiemetic, antipsychotic, antihistaminic, and anticholinergic activities in the human body.

Examples of Phenothiazine Drugs

1. Antipsychotics: Chlorpromazine, Fluphenazine, Mesoridazine, Prochlorperazine, Perphenazine, Trifluoperazine, and Thioridazine.

2. Other Examples: Antiverm, Biverm, Dibenzothiazine, Vermitin, Fentiazine, Contaverm, Fenothiazine, Phenovarm, Helmetine, Penthazine, Phenovis, and Nemazene.

Formulation of Various Phenothiazine Drugs

In general, phenothiazine drugs are available in oral tablets. But, there are other forms of administration drugs. These are

  • Prochlorperazine is available as a rectal suppository.
  • Fluphenazine and mesoridazine are available as injections.

Structure and Synthesis of Phenothiazine


As stated earlier, It is related to the thiazine class of heterocyclic compounds which basically resembles the 3 benzene ring but with some modification i.e. the middle ring is constitute with Sulphur and nitrogenous compound (C4SN).

Here is how it looks at the 2D normal scale.

 Phenothiazine's Structure and Synthesis


Phenothiazine was formally prepared by the reaction of diphenylamine with sulfur. In this reaction, diphenylamine is fused with sulfur under the iodine catalyst to yield Phenothiazine.

But due to lack of yielding potential, this mechanism of production not gets in the industry phase. To compensate this, a new cyclization of 2-substituted diphenyl sulfides are currently employed for industry-level production of this drug.

As from now, you know there are various derivatives of Phenothiazines which are generally prepared from various pharmaceutical measures.

However, the most common way of preparing their derivatives is through charge transfer salts that extract the electron from Phenothiazines and formed the desired compound.

Mechanism of Action on the Human Body

In all Phenothiazines drugs, one thing is common i.e., they stimulate the dopamine D2-receptor by triggering the Chemoreceptor Trigger Zone (CTZ) of the brain. As a result, they prevent chemotherapy-induced emesis (vomit).

Mechanism of Action on the Human Body

Although, they are not only responsible for stimulating dopamine receptors but also alters the peripheral and central antagonistic activity by imitating the serotonergic, histaminic, and muscarinic receptors of the human brain.

Uses of Phenothiazines

We classify Phenothiazines drug based on their type of uses which are listed below:

Phenothiazines' uses
Uses of Phenothiazines

Former Uses of Phenothiazines

In the early 1900s, they are used to be an insecticide. In addition, they are also used to kill the infectious parasitic worms in both humans and animals.

But in 1935, an insecticide product by DuPont was sold for about 3.5 million dollars. However, they tend to degrade in sunlight and air. As a result, it became difficult to determine the quantity of their use in the field. And with the arrival of DDT, that product loses its value.

In the 1940s, Phenothiazines derivatives were used as anthelminthic (antiparasitic drugs) for both livestock and humans but later in the 1950s, the drug was replaced by other drugs.

Phenothiazine-Derived Drugs

With the introduction of methylene blue derivative of Phenothiazine which in the 1880s were used as a novel prize experiment by Paul Ehrlich that helps him to discovers the different cell types.

While later in the 1890s, these are used for suppressing the condition of malaria. And in the 1950s, the scientist derived a strong effect of Phenothiazines derivatives on psychiatry.

In addition, with the development of modern science, Phenothiazine shows other characteristics which again classified into four main classes. These are antiemetic, antipsychotic, antihistaminic, and anticholinergic

However, strictly talking about Phenothiazine antipsychotics,  they are classified into three groups that differ with respect to the substituent of nitrogen. These are

  • Aliphatic compounds (bearing acyclic groups)
  • Piperidines (bearing piperidine-derived groups)
  • Piperazine (bearing piperazine-derived substituents).

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Non-Drug Applications

The drug —methylene blue can also be used as a water-soluble synthetic dye. There are many color variants available for Phenothiazine synthetic drugs are named as methylene blue, methylene green, and thionine.

All those methylene synthetics dyes can be used as electrocatalyst for NADH oxidation for the production of biosensors and biofuel cells.

Apart from this, Phenothiazine can be used as an anaerobic inhibitor for the purification of various acids like acrylic acid.

Side effects of Phenothiazine

The effects of Phenothiazine are usually affected by the condition of both the human body and also their use with other drugs.

Common Side Effects

effects of Phenothiazine
Side effects of Phenothiazine

Here are the common side effects of phenothiazine antipsychotics.

  • Drowsiness,
  • Dizziness,
  • Headache,
  • Low BP (Blood Pressure)
  • Blurred Vision.

Extra-Pyramidal Symptoms

These are the list of extrapyramidal symptoms that are caused by Phenothiazines.

  • Abnormal Muscle Contractions
  • Difficulty in breathing
  • Swallowing necks
  • Neck spasms
  • Pain in parts of face, arms, and legs.
  • Constipation (common)

Neuroleptic Malignant Syndrome (NMS)

The other side effects are Phenothiazine that can cause NMS that have symptoms like;

  • Fever
  • Muscle rigidity
  • Altered mental status
  • Irregular blood pressure
  • Irregular heart rate and rhythm

Precautions While using Phenothiazine 

  • Phenothiazine drugs should be used based on prescribed prescriptions.
  • It should not be combined with other antipsychotics or medications. Because it increases the chance of extrapyramidal side effects and NMs syndrome.


  • Should be used with caution when the patient is already on medication such as Prozac, Sarafem, Prozac. They can reduce the activity of liver enzymes which further increase the side effects of phenothiazines.
  • Drugs like amiodarone, fluconazole, and itraconazole (many others), when used with Phenothiazines, can alter the heart rate and sometimes cause abnormal heart rate.

Note: All phenothiazine antipsychotics have a boxed warning of deaths in the case of dementia-related psychosis. These are commonly seen in elderly aged people.

Phenothiazine Drugs During Pregnancy

Till now, there is no conclusive research related to the effects of Phenothiazines during pregnancy. However, as per the researcher’s theory, Phenothiazine when exposed to later months of pregnancy, can increase the risk of extrapyramidal side effects.

Phenothiazine Drugs during Pregnancy

Therefore, it is advisable that Phenothiazine drugs should be only used when they are needed the most.

While talking about breastfeeding, Phenothiazine has a tendency to enters breast milk. Hence again, precautions should be taken when prescribing phenothiazine drugs to a new child’s mother.


We had started from the overview of phenothiazine where we have discussed various types of phenothiazine drugs along with examples and their formulations. After that, we switched to the synthesis part of Phenothiazines and how it affects the human body.

Our next major topic related to Phenothiazine drug was its uses that are coupled with side effects. And finally, we ended the article with the precaution and special case of pregnancy.

Therefore, we have reviewed all the information related to Phenothiazine.

General FAQs

1. Why are phenothiazines so dangerous?
Ans. Because they produce the dangerous hypersensitivity reactions of agranulocytosis (severe and dangerous leukopenia), hepatitis, and dermatitis (etching skin). And accidental overdose in children leads to severe central nervous system failure.

2. Is phenothiazine a sedative?
Ans. Phenothiazines do not possess any sedative effects unless combined with other analgesic drugs like opioids.

3. What are the serious and irreversible side effects of phenothiazines?
Ans. Phenothiazines can cause permanent tardive dystonia (muscle movement disorders) and liver damages.

4. What are the contraindications of promethazine?
Ans. They act as a comatose causer (serve central nervous system depression) that again malfunctions the normal working of the human body.

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