Phenothiazine is the organic compound with the formula S(C6H4)2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related the thiazine-class of heterocyclic compounds. Derivatives of the parent compound find wide use as drugs.
The compound was originally prepared by Bernthsen in 1883 via the reaction of diphenylamine
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.
The synthetic dye methylene blue
, containing the structure, was described in 1876. Phenothiazine itself was introduced by DuPont
as an insecticide
. It is sometimes used as an antihelminthic
The phenothiazine structure occurs in various neuroleptic
drugs, e.g. Chlorpromazine
, 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 akathisia
, tardive dyskinesia
, extrapyramidal symptoms
, 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 compounds (bearing acyclic groups), the "piperidines" (bearing piperidine-derived groups), and the piperazine (bearing piperazine-derived substituents).
||Extrapyramidal side-effect |
| Aliphatic compounds
||Chlorpromazine (marketed as Thorazine, Chlor-PZ, Klorazine, Promachlor, Promapar, Sonazine, Chlorprom, Chlor-Promanyl, Largactil)
|Promazine (trade name Sparine)
|Triflupromazine (trade names Stelazine, Clinazine, Novaflurazine, Pentazine, Terfluzine, Triflurin, Vesprin)
|Levomepromazine in Germany and Methotrimeprazine in America (trade names Nozinan, Levoprome)
||Mesoridazine (trade name Serentil)
|Thioridazine (trade names Mellaril, Novoridazine, Thioril)
||Fluphenazine (trade names Prolixin, Permitil, Modecate, Moditen)
|Perphenazine (sold as Trilafon, Etrafon, Triavil, Phenazine)
|Flupentixol (sold as Depixol, Fluanxol)
|Prochlorperazine (trade names Compazine, Stemetil) |
|Trifluoperazine (trade name Stelazine)
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.