Phenothiazine
Encyclopedia
Phenothiazine is an organic compound
that occurs in various antipsychotic
and antihistaminic drugs. It has the formula S(C6H4)2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine
-class of heterocyclic compound
s. Derivatives of the parent compound find wide use as drugs.
with sulfur, but more recent syntheses rely on the cyclization of 2-substituted diphenylsulfide. The pharmaceutically significant derivatives of phenothiazine are not prepared from phenothiazine.
, containing the structure, was described in 1876. Phenothiazine itself was introduced by DuPont
as an insecticide
in 1935. It is sometimes used as an antihelminthic in livestock.
In the manufacture of monomers, Phenothiazine is used as a chemical stabilizer
or inhibitor
to prolong storage and shelf life of products like acryloyl chloride.
Many water soluble phenothiazine derivatives such as methylene blue
, methylene green
, thionine, and others are able to be electropolymerized into conductive polymers that are used as electrocatalyst
s for NADH oxidation in enzymatic biosensors and biofuel cells. ,,
, and antihistaminic drugs, e.g. promethazine
. The term "phenothiazines" describes the largest of the five main classes of neuroleptic antipsychotic drugs
. These drugs have antipsychotic and, often, antiemetic
properties, although they may also cause severe side effects
such as extrapyramidal symptoms
(including akathisia
and tardive dyskinesia
), hyperprolactinaemia
, and the rare but potentially fatal neuroleptic malignant syndrome
as well as substantial weight gain.
Phenothiazines are used as inodilators in congestive heart failure
, acting upon the type I calcium/calmodulin dependent phosphodiesterase
.
Phenothiazine antipsychotics are classified into three groups that differ with respect to the substituent on nitrogen: the aliphatic compound
s (bearing acyclic groups), the "piperidines" (bearing piperidine
-derived groups), and the piperazine (bearing piperazine
-derived substituents).
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
that occurs in various antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
and antihistaminic drugs. It has the formula S(C6H4)2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine
Thiazine
Thiazines are organic compounds containing a ring of four carbon, one nitrogen and one sulfur atom. Chemicals that include thiazine are used for dyes, tranquilizers and insecticides.-See also:*Methylene blue*Phenothiazine*Heterocyclic compound*Morpholine...
-class of heterocyclic compound
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....
s. Derivatives of the parent compound find wide use as drugs.
Synthesis
The compound was originally prepared by Bernthsen in 1883 via the reaction of diphenylamineDiphenylamine
Diphenylamine is the organic compound with the formula 2NH. It is a colourless solid, but samples are often yellow due to oxidized impurities.-Preparation and reactivity:...
with sulfur, but more recent syntheses rely on the cyclization of 2-substituted diphenylsulfide. The pharmaceutically significant derivatives of phenothiazine are not prepared from phenothiazine.
Non-drug applications
The synthetic dye methylene blueMethylene blue
Methylene blue is a heterocyclic aromatic chemical compound with the molecular formula C16H18N3SCl. It has many uses in a range of different fields, such as biology and chemistry. At room temperature it appears as a solid, odorless, dark green powder, that yields a blue solution when dissolved in...
, containing the structure, was described in 1876. Phenothiazine itself was introduced by DuPont
DuPont
E. I. du Pont de Nemours and Company , commonly referred to as DuPont, is an American chemical company that was founded in July 1802 as a gunpowder mill by Eleuthère Irénée du Pont. DuPont was the world's third largest chemical company based on market capitalization and ninth based on revenue in 2009...
as an insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
in 1935. It is sometimes used as an antihelminthic in livestock.
In the manufacture of monomers, Phenothiazine is used as a chemical stabilizer
Stabilizer (chemistry)
In chemistry a stabilizer is a chemical which tends to inhibit the reaction between two or more other chemicals. It can be thought of as the antonym to a catalyst...
or inhibitor
Inhibitor
Something that restrains, blocks, or suppresses.Inhibitor or inhibition may refer to:* Corrosion inhibitor, a substance that decreases the rate of metal oxidation...
to prolong storage and shelf life of products like acryloyl chloride.
Many water soluble phenothiazine derivatives such as methylene blue
Methylene blue
Methylene blue is a heterocyclic aromatic chemical compound with the molecular formula C16H18N3SCl. It has many uses in a range of different fields, such as biology and chemistry. At room temperature it appears as a solid, odorless, dark green powder, that yields a blue solution when dissolved in...
, methylene green
Methylene green
Methylene green is a heterocyclic aromatic chemical compound similar to methylene blue. It is used as a dye.- External links :*...
, thionine, and others are able to be electropolymerized into conductive polymers that are used as electrocatalyst
Electrocatalyst
An electrocatalyst is a catalyst that participates in electrochemical reactions. Catalyst materials modify and increase the rate of chemical reactions without being consumed in the process. Electrocatalysts are a specific form of catalysts that function at electrode surfaces or may be the...
s for NADH oxidation in enzymatic biosensors and biofuel cells. ,,
Phenothiazine-derived drugs
The phenothiazine structure occurs in various neuroleptic drugs, e.g. chlorpromazineChlorpromazine
Chlorpromazine is a typical antipsychotic...
, and antihistaminic drugs, e.g. promethazine
Promethazine
Promethazine is a first-generation antihistamine of the phenothiazine family. The drug has anti-motion sickness, antiemetic, and anticholinergic effects, as well as a strong sedative effect and in some countries is prescribed for insomnia when benzodiazepines are contraindicated...
. The term "phenothiazines" describes the largest of the five main classes of neuroleptic antipsychotic drugs
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
. These drugs have antipsychotic and, often, antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
properties, although they may also cause severe side effects
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
such as extrapyramidal symptoms
Extrapyramidal symptoms
The extrapyramidal system can be affected in a number of ways, which are revealed in a range of extrapyramidal symptoms , also known as extrapyramidal side-effects , such as akinesia and akathisia .Extrapyramidal symptoms are various movement disorders such as acute dystonic reactions,...
(including akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
and tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
), hyperprolactinaemia
Hyperprolactinaemia
Hyperprolactinaemia or hyperprolactinemia is the presence of abnormally-high levels of prolactin in the blood. Normal levels are less than 500 mIU/L for women, and less than 450 mIU/L for men....
, and the rare but potentially fatal neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
as well as substantial weight gain.
Phenothiazines are used as inodilators in congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, acting upon the type I calcium/calmodulin dependent phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
.
Phenothiazine antipsychotics are classified into three groups that differ with respect to the substituent on nitrogen: the aliphatic compound
Aliphatic compound
In organic chemistry, aliphatic compounds are acyclic or cyclic, non-aromatic carbon compounds.Thus, aliphatic compounds are opposite to aromatic compounds.- Structure :...
s (bearing acyclic groups), the "piperidines" (bearing piperidine
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
-derived groups), and the piperazine (bearing piperazine
Piperazine
Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste....
-derived substituents).
| Group | Autonomic Autonomic nervous system The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,... |
Example | Sedative | Extrapyramidal side-effect |
| Aliphatic compound Aliphatic compound In organic chemistry, aliphatic compounds are acyclic or cyclic, non-aromatic carbon compounds.Thus, aliphatic compounds are opposite to aromatic compounds.- Structure :... s |
||||
| moderate | Chlorpromazine Chlorpromazine Chlorpromazine is a typical antipsychotic... (marketed as Thorazine, Chlor-PZ, Klorazine, Promachlor, Promapar, Sonazine, Chlorprom, Chlor-Promanyl, Largactil) |
strong | moderate | |
| Promazine Promazine Promazine is a medication that belongs to the phenothiazine class of antipsychotics. An older medication used to treat schizophrenia, it is still prescribed, alongside newer agents such as olanzapine and quetiapine... (trade name Sparine) |
moderate | moderate | ||
| Triflupromazine Triflupromazine Triflupromazine is an antipsychotic medication of the phenothiazine class. Among different effects of triflupromazine indication for use of this drug is severe emesis... (trade names Stelazine, Clinazine, Novaflurazine, Pentazine, Terfluzine, Triflurin, Vesprin) |
strong | moderate/strong | ||
| Levomepromazine Levomepromazine Levomepromazine in Germany and Methotrimeprazine in America is an aliphatic phenothiazine neuroleptic drug... in Germany and Methotrimeprazine in America (trade names Nozinan, Levoprome) |
extremely strong | low | ||
| Piperidines | strong | Mesoridazine Mesoridazine Mesoridazine is a piperidine neuroleptic drug belonging to the class of drugs called phenothiazines, used in the treatment of schizophrenia. It is a metabolite of thioridazine... (trade name Serentil) |
strong | weak |
| Thioridazine Thioridazine Thioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis... (trade names Mellaril, Novoridazine, Thioril) |
strong | weak | ||
| Piperazines | weak | Fluphenazine Fluphenazine Fluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines.... (trade names Prolixin, Permitil, Modecate, Moditen) |
weak/moderate | strong |
| Perphenazine Perphenazine Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades.... (sold as Trilafon, Etrafon, Triavil, Phenazine) |
weak/moderate | strong | ||
| Prochlorperazine Prochlorperazine Prochlorperazine is a dopamine receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly-potent typical antipsychotic, 10-20x more potent than chlorpromazine... (trade names Compazine, Stemetil) |
||||
| Trifluoperazine Trifluoperazine Trifluoperazine is a typical antipsychotic of the phenothiazine chemical class.- Uses :... (trade name Stelazine) |
moderate | strong |
Appendix: tradenames for phenothiazine
Like many commercially significant compounds, phenothiazine has numerous trade names including AFI-Tiazin; Agrazine; Antiverm; Biverm; Dibenzothiazine; Orimon; Lethelmin; Souframine; Nemazene; Vermitin; Padophene; Fenoverm; Fentiazine; Contaverm; Fenothiazine; Phenovarm; Ieeno; ENT 38; Helmetina; Helmetine, Penthazine; XL-50; Wurm-thional; Phenegic; Phenovis; Phenoxur; Reconox.Further reading
- MSDS
- Hendricks, Christensen, J.B., and Kristiansen, Jette E. Sonderborg, Denmark. "Antibakterielle Eigenschaften der Phenothiazine: Eine Behandlungsoption für die Zukunft?" Chemotherapie Journal. 13.5. (2004): 203–205. Wissenschaftliche Verlagsgesesellschaft mbH. 21 August 2005. (PDF).
- PubChem Substance Summary: Phenothiazine National Center for Biotechnology Information.