Phenothiazine is a class of agents exhibiting antiemetic, antipsychotic, antihistaminic, and anticholinergic activities. Phenothiazines antagonize the dopamine D2-receptor in the chemoreceptor trigger zone (CTZ) of the brain, potentially preventing chemotherapy-induced emesis. In addition, these agents have peripherally or centrally antagonistic activity against alpha adrenergic, serotonergic, histaminic, and muscarinic receptors.
Phenothiazines are used to treat serious mental and emotional disorders, including schizophrenia and other psychotic disorders. Some are used also to control agitation in certain patients, severe nausea and vomiting, severe hiccups, and moderate to severe pain in some hospitalized patients. Chlorpromazine is used also in the treatment of certain types of porphyria, and with other medicines in the treatment of tetanus. Phenothiazines may also be used for other conditions as determined by your doctor.
It is clean gray-green powder with the melting point of 185.5 ℃, boiling point of 371 ℃, 290 ℃ (5.33kPa). It is insoluble in petroleum ether, chloroform and water, and soluble in ether and hot acetic acid. It will be oxidized upon exposure to light in the air.
For more than a decade, phenothiazine drugs have been used to treat a variety of disorders and have proved particularly effective in the treatment of schizophrenia. Clinical experience indicates that initial extremely high dosages are necessary to effect improvement of patients with schizophrenic illnesses.
During 1964, several sequelae have been reported following prolonged high dosage of these drugs. These recent reports refer to side effects which are apparently permanent, in contrast to earlier communications of transient deleterious effects. For example, it has been known for several years that extrapyramidal disorders occur frequently in patients taking phenothiazines; however, a reduction in dosage or cessation of medication appeared to produce a return to the normal state.
Phenothiazines may cause unwanted, unattractive, and uncontrolled face or body movements that may not go away when you stop taking the medicine. They may also cause other serious unwanted effects. You and your doctor should talk about the good this medicine will do as well as the risks of using it. Also, your doctor should look for early signs of these effects at regular visits. Your doctor may be able to stop or decrease some unwanted effects, if they do occur, by changing your dose or by making other changes in your treatment.
These medicines are available only with your doctor's prescription.
Levoprome(R) (methotrimeprazine) is no longer available in the United States. At the end of May 1998, Immunex Corporation stopped marketing it.
Once a medicine has been approved for marketing for a certain use, experience may show that it also is useful for other medical problems. Although these uses are not included in product labeling, phenothiazines are used in certain patients with the following medical conditions:
- Chronic neurogenic pain (certain continuing pain conditions)
- Huntington's chorea (hereditary movement disorder)
- Migraine headaches
- Phenothiazine is a relatively widely used anthelmintic reagent with excellent efficacy in treating the Haemonchus contortus of cattle, horse and sheep, nodular worm, Bunostomum and Plasmodium chabaudi.
- Phenothiazine is the intermediates of fine chemicals such as dyes and drugs with itself being a auxiliary material for synthetic material (the anti-polymerization reagent for production of vinylon), fruit pesticides and veterinary anthelmintic.
- It is mainly used as the polymerization inhibitor for acrylic acid, acrylic esters, and methacrylic aicd as well as ester monomer.
22 g of diphenylamine, 8.2 g of sulfur, and 3.2 gms. of anhydrous aluminum chloride are melted together. The reaction sets 140-150° C with the rapid evolution of hydrogen sulfide; by lowerg the temperature, a few degrees the reaction can be slackened. Wen the reaction has moderated, the temperature is raised to 160° C for a time. The melt, when cool, is ground up and extracted, first with water and then with dilute alcohol. The residue consists of almost pure phenothiazine. It can be recrystallised from alcohol. Yield 93%, yellowish leaflets; m.p. 180° C.
Systematic organic chemistry, by W. M. Cumming, 325-326, 1937.
Phenothiazine was initially synthesized in 1883 by Bernthsen.
It was the basis for the development of other drugs including
the phenothiazine class of antipsychotics or neuroleptics.
Phenothiazines are the largest class of neuroleptics and
include agents such as chlorpromazine, thioridazine, and
prochlorperazine. In 1933, a derivative of phenothiazine,
promethazine, was synthesized. It was found to have much
more significant sedative and antihistaminic effects than
previous derivatives of phenothiazine and it was used to
induce sedation for surgical patients. After promethazine was
developed, a series of agents, including chlorpromazine, was
synthesized and tested in France at a military hospital by the
French physician Laborit. Laborit found that chlorpromazine
induced calm in patients and had other effects that might be useful clinically. Chlorpromazine, known colloquially as
‘Laborit’s drug’ was released into the market in 1953 after
a trial published in 1952 showed efficacy in treatment of
psychosis in 38 individuals who received daily injections of
chlorpromazine. Chlorpromazine is the prototypical drug for
the phenothiazine class of antipsychotics. The phenothiazines
are classified as low-potency antipsychotics and have more
side effects at standard doses than the newer agents used as
neuroleptics. For example, they are more anticholinergic and
have more extrapyramidal effect than newer agents.
yellow or pale green powder
Phenothiazine is a greenish-yellow to greenish-gray crystalline substance. Slight odor and taste.
A key component of antipsychotic and antihistaminic drugs.
Employed in the preparation of carbazoles and piperazines,1 and charge-transfer semiconducting complexes.2
A rigid, tricyclic thiazine useful as an electron donor.
Phenothiazines are neuroleptic agents that affect a variety of
receptors including dopaminergic receptor sites. Phenothiazines
are used to treat psychosis including schizophrenia;
violent, agitated, disturbed behavior; and mania secondary to
bipolar disorder. Other uses include treatment of pain, headache,
hiccups, acute severe anxiety, idiopathic dystonia,
withdrawal, taste disorders, leishmaniasis, acute intermittent
porphyria, and alleviation of nausea and vomiting.
Phenothiazines allow smoother induction of anesthesia,
potentiate anesthetic agents, and treat behavioral symptoms
secondary to Alzheimer disease and senile dementia. Some
phenothiazines exert an antipruritic effect and are useful for
the treatment of neurodermatitis and pruriginous eczema, and
relieve psychogenic itching.
Insecticide; manufacture of pharmaceuticals.
ChEBI: The 10H-tautomer of phenothiazine.
Light green to steel-blue powder. Acquires a greenish-brown tint under exposure to sunlight.
Phenothiazine is slowly decomposed by sunlight. . Organosulfides are incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials generate heat and in many cases hydrogen gas. Many of these compounds may liberate hydrogen sulfide upon decomposition or reaction with an acid.
Flash point data for Phenothiazine are not available, but Phenothiazine is probably combustible.
Flammability and Explosibility
Non flammable
Poison by intravenous route. Moderately toxic to humans by ingestion. Experimental reproductive effects. An insecticide. Large doses, i.e., heavy exposure, may cause hemolytic anemia and toxic degeneration of the liver. Can cause skin irritation and photosensitization. Dangerous; when heated to decomposition or on contact with acid or acid fumes it emits hghly toxic fumes of SOx and NOx.
Phenothiazine is used as an insecticide; as a base for the manufacture of tranquilizers; as anthelmintic in medicine and veterinary medicine; it is used widely as an intermediate in pharmaceutical manufacture; polymerization inhibitor, antioxidant.
Physicochemical Properties
Phenothiazine has the standard formula S(C6H4)2NH and
includes a tricyclic structure that is related to the thiazines.
Thiazines are used in the manufacture of synthetic dies.
Chlorpromazine
Chlorpromazine is a white to off-white substance (both the base
and the hydrochloride salt) that is a powder or waxy solid as
a base and a crystalline powder as the hydrochloride. Chlorpromazine
is odorless or has a slightly amine-like odor. It has
a melting point of 56–58 °C and in the basic form is practically
insoluble in water, soluble in alcohol, and less soluble in chloroform
and ether. It is freely soluble in dilute mineral acids. As
the hydrochloride salt, chlorpromazine is soluble in water, less
soluble in alcohol and chloroform, and insoluble in ether. A
10% aqueous solution has a pH of 3.5–4.5.
UN3077 Environmentally hazardous substances, solid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous hazardous material, Technical Name Required
Crystallise it from *benzene, toluene, hexane or Me2CO (charcoal) after boiling for 10minutes under reflux. Filter the crystals off and dry them in an oven at 100o, then in a vacuum desiccator over paraffin chips. Also recrystallise it twice from water and dry it in an oven at 100o for 8-10hours. It sublimes at 130o/1mm and has UV with at 253nm in heptane. [Beilstein
Phenothiazines primarily block postsynaptic neurotransmission
by binding to dopamine (D1 and D2), muscarinic, histamine H1,
and serotonergic 5-HT2 receptors. Phenothiazines also possess
peripheral adrenergic receptor blockade and quinidine-like
cardiac effects. Phenothiazines may lower the seizure threshold.
Organosulfides are incompatible with strong acids and acid fumes; elevated temperatures; sulfur oxides and nitrogen oxides can be produced. Contact with strong reducing agents such as hydrides; azo and diazo compounds, halocarbons, isocyanates can generate heat and may form explosive hydrogen gas
Dissolve in combustible solvent and spray into incinerator equipped with afterburner and scrubber. In accordance with 40CFR165, follow recommendations for the disposal of pesticides and pesticide containers. Must be disposed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office.
