What is Phenothiazine?
Alternately known as PTZ, phenothiazine is an organic compound with the chemical formula – S(C6H4)2NH. The compound has a connection to the thiazine class of heterocyclic compounds. The derivatives of phenothiazine are highly bioactive. They also have a history of widespread use. The phenothiazine class of organic compounds exhibits antiemetic, antipsychotic, antihistaminic, and anticholinergic properties. The derivatives of phenothiazine are genuinely revolutionary as many of them have usages in life-saving medicinal drugs. In medical chemistry, phenothiazine is a prototypical pharmaceutical lead structure.
Properties of Phenothiazine
The colour of phenothiazine is a light green to steel-blue powder, and it acquires a greenish-blue tint when exposed to sunlight.
The compound does not have any taste, and the odour is slightly pungent.
The melting point of phenothiazine from 365.9 degrees Fahrenheit to 366.6 degrees Fahrenheit.
Phenothiazine is freely soluble in Benzene and hot acetic acid.
It is slightly soluble in alcohol and mineral oils.
The compound is practically insoluble in petroleum ether and chloroform.
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Uses of Phenothiazine
Even after comprehensive research, phenothiazine uses only have theoretical interests. The phenothiazine derivatives have ground-breaking applications in fields of medicine like psychiatry, anaesthetics, and pest management. Some derivatives have applications in advanced batteries and fuel cells. Many of phenothiazine's water-soluble derivatives like methylene blue, methylene green, thionine, etc., can be electropolymerized into conductive polymers used as electrocatalysts NADH oxidation in enzymatic biosensors and biofuel cells. Phenothiazine also has utilisation as an anaerobic restrictor for acrylic acid polymerisation. It is often used as an in-process inhibitor during the purification of acrylic acid.
Formerly, phenothiazine was used as an insecticide and drug to treat infections with parasitic worms in livestock and people. But, now, its application for these purposes has been superseded by other more prominent chemicals.
It was DuPont who first introduced phenothiazine as an insecticide in 1935. The USA sold about 3,500,000 pounds in 1944. However, as phenothiazine deteriorates in sunlight and air, its usage declined as a pesticide from the 1940s. With the arrival of better alternatives like DDT in the market, phenothiazine lost its significance as a pest controller. DDT was more durable and practical as a positive during those times.
Phenothiazine was introduced as an anthelmintic in livestock during the 1940s. It is considered the world's first modern anthelmintic, along with thiabendazole.
In the 1940s, phenothiazine also was used as an anthelmintic for human beings. Other drugs superseded phenothiazine in the 1950s.
The phenothiazine derivatives treat psychosis, including schizophrenia, violent, agitated, disturbed behaviour, and the manic phase of bipolar disorder. Other applications include painkillers, curing headache, hiccups, anxiety, idiopathic dystonia, withdrawal, taste disorders, leishmaniasis, alleviation of nausea and vomiting and acute intermittent porphyria. Phenothiazines permit smoother induction of anaesthetic agents and allow treatment of behavioural symptoms secondary to Alzheimer’s and senile dementia. Some phenothiazines exert an antipruritic effect. They are helpful for the treatment of neurodermatitis and pruriginous eczema and may relieve psychogenic itching.
The Medical Use of Phenothiazine
Heinrich Caro first synthesised methylene blue – a derivative of phenothiazine in 1876. Methylene blue was used by Paul Ehrlich during the mid-1880s in his cell staining experiments that consequently lead to his pioneering discoveries on cell types. Ehrlich asserts that methylene blue could also be used to treat malaria, and he tested it clinically. Due to concerted efforts, Ehrlich discovered malaria's cure, and methylene blue was being used for that purpose since the 1890S.
From the 1940s, research on phenothiazine derivatives expanded, and chemists working with Paul Charpentier at Rhone-Poulenc Laboratories in Paris began making derivatives of the same. Such efforts revealed that although phenothiazine had no activity against organisms, it had appropriate antihistamine activities with a powerful sedative effect. Phenothiazine went into the market as a drug for allergies and anaesthesia. From the 1940s onwards, experts realised that the same lab-produced chlorpromazine had an even more potent sedative and soothing effect. Pioneers Jean Delay and Pierre Deniker began using it on psychiatric patients and published their findings in the early part of the 1950s. The robust results they yielded opened the door of modern psychiatry and led to the mushrooming of work on phenothiazine medications.
The word "phenothiazines" infers the biggest of the five primary classes of antipsychotic medicines. These drugs have antipsychotic elements and also antiemetic properties.
Phenothiazine Antipsychotics are Grouped into Three Categories that differ Concerning the Substituent on Nitrogen:
The aliphatic compounds
The "piperidines."
The piperazine
It is imperative to also remember the side effects of phenothiazine that range from extrapyramidal signs to weight gain and the fatal neuroleptic malignant syndrome. Some people may also develop tartrazine allergy in phenothiazine derivatives. Tartrazine is the most commonly used dye in psychotropic drugs and has proven to cause allergic reactions among a large number of people.
Conclusion
The topic of phenothiazine may seem very tricky to grasp. The concept does get manageable with thorough understanding, regularly solving questions and numerical, practising papers and proper revision. Before trying to understand the whole concept, we must grasp the basics of phenothiazine then move to its uses, medical applications, synthesis, and side effects and so on. Brushing up the basics of Chemistry always helps in learning challenging concepts. After learning the fundamentals of phenothiazine, it is imperative to learn about its class and structure as well.
FAQs on Phenothiazine
1. What is phenothiazine and why is it important in medicine?
Phenothiazine is an organic compound that forms the core chemical structure for a major class of drugs, particularly tranquilizers. Its medical importance comes from its derivatives, which were among the first effective medications for treating severe mental health conditions like psychosis and schizophrenia. Additionally, these derivatives are widely used as antiemetics to prevent nausea and as antihistamines.
2. What are some common examples of phenothiazine-based drugs?
Several important drugs are derived from the phenothiazine structure. Key examples mentioned in the CBSE syllabus context include:
- Chlorpromazine: A typical tranquilizer and one of the earliest discovered antipsychotic drugs.
- Prochlorperazine: Primarily used to treat severe nausea, vomiting, and anxiety.
- Promethazine: Known for its strong antihistamine effects in treating allergies, and also used as a sedative.
- Fluphenazine: A high-potency antipsychotic for managing chronic schizophrenia.
3. How do phenothiazine drugs work in the brain?
Phenothiazines function primarily by acting as antagonists to dopamine receptors (specifically the D2 subtype) in the brain. Dopamine is a key neurotransmitter that regulates mood, thought processes, and perception. By blocking its action, these drugs help to reduce the excessive dopaminergic activity that is linked to psychotic symptoms such as hallucinations and delusions.
4. What are the major side effects associated with phenothiazine use?
While effective, phenothiazines can cause significant side effects by affecting the nervous system. The most notable ones include:
- Extrapyramidal Symptoms (EPS): These are movement-related disorders, including muscle stiffness, tremors, and a state of restlessness known as akathisia.
- Tardive Dyskinesia: A more severe, potentially irreversible condition characterized by involuntary, repetitive movements of the face and body.
- Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening reaction that causes high fever, severe muscle rigidity, and confusion.
- Other common effects can include drowsiness, weight gain, and dry mouth.
5. How does the chemical structure of phenothiazine relate to its function as a drug?
The function of a phenothiazine drug is critically dependent on its chemical structure. The core is a three-ring system, but the specific therapeutic effect is determined by the chemical side chain attached to its nitrogen atom. Modifying this side chain allows chemists to fine-tune the drug's properties, enhancing its antipsychotic, antiemetic, or antihistaminic effects. This structure-activity relationship is fundamental to creating different drugs for different medical needs from the same basic molecule.
6. Why do phenothiazines cause movement-related side effects like tremors?
The movement-related side effects occur because phenothiazines are not perfectly selective in their action. While they target dopamine pathways to treat psychosis, they also inadvertently block dopamine receptors in the nigrostriatal pathway of the brain. This pathway is essential for regulating smooth and controlled motor functions. Disrupting the dopamine balance here leads to the Parkinson's-like symptoms, such as tremors and rigidity, known as extrapyramidal side effects.
7. How are phenothiazine drugs classified for medical use?
Phenothiazines are generally classified into three groups based on the side chain attached to their nitrogen atom, which influences their potency and side effect profile:
- Aliphatic compounds (e.g., Chlorpromazine): Known for moderate antipsychotic effects but strong sedative properties.
- Piperidine compounds (e.g., Thioridazine): Have lower antipsychotic potency and fewer movement-related side effects but may carry other risks.
- Piperazine compounds (e.g., Fluphenazine): These are the most potent antipsychotics but also have the highest risk of causing extrapyramidal side effects.
8. Beyond psychosis, what are other important applications of phenothiazine derivatives?
The versatility of phenothiazine derivatives extends well beyond treating psychosis. Their other significant medical uses include:
- As antiemetics: They are highly effective in controlling severe nausea and vomiting resulting from chemotherapy, surgery, or motion sickness.
- As antihistamines: Certain derivatives like Promethazine are powerful antihistamines used for allergic reactions and as sedatives.
- In veterinary medicine: Drugs like Acepromazine are used to sedate animals before surgery or during transport.
