Phenothiazine

Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. The derivatives chlorpromazine and promethazine revolutionized the field of psychiatry and allergy treatment., respectively. An earlier derivative, methylene blue, was one of the first antimalarial drugs, and derivatives are under investigation as possible anti-infective drugs. Phenothiazine is a prototypical pharmaceutical lead structure in medicinal chemistry. Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. The derivatives chlorpromazine and promethazine revolutionized the field of psychiatry and allergy treatment., respectively. An earlier derivative, methylene blue, was one of the first antimalarial drugs, and derivatives are under investigation as possible anti-infective drugs. Phenothiazine is a prototypical pharmaceutical lead structure in medicinal chemistry. Phenothiazine itself is only of theoretical interest, but its derivatives revolutionized psychiatry, other fields of medicine, and pest management. Other derivatives have been studied for possible use in advanced batteries and fuel cells. In 1876, methylene blue, a derivative of phenothiazine, was synthesized by Heinrich Caro at BASF. The structure was deduced in 1885 by Heinrich August Bernthsen. Bernthsen synthesized phenothiazine in 1883. In the mid 1880s, Paul Ehrlich began to use methylene blue in his cell staining experiments that led to pioneering discoveries about different cell types. He was awarded a Nobel Prize based in part on that work. He became particularly interested in its use to stain bacteria and parasites such as Plasmodiidae – the genus that includes the malaria pathogen – and found that it could be stained with methylene blue. He thought methylene blue could possibly be used in the treatment of malaria, tested it clinically, and by the 1890s methylene blue was being used for that purpose. For the next several decades, research on derivatives lapsed until phenothiazine itself came to market as an insecticide and deworming drug. In the 1940s, chemists working with Paul Charpentier at Rhone-Poulenc Laboratories in Paris (a precursor company to Sanofi), began making derivatives. This work led to promethazine which had no activity against infective organisms, but did have good antihistamine activity, with a strong sedative effect. It went to market as a drug for allergies and for anesthesia. As of 2012 it was still on the market. At the end of the 1940s the same lab produced chlorpromazine which had an even stronger sedative and soothing effect, and Jean Delay and Pierre Deniker attempted to use it on their psychiatric patients, publishing their results in the early 1950s. The strong effects they found opened the door of the modern field of psychiatry and led to a proliferation of work on phenothiazine derivatives. The systematic research conducted by chemists to explore phenothiazine derivatives and their activity was a pioneering example of medicinal chemistry; phenothiazine is often discussed as a prototypical example of a pharmaceutical lead structure. The term 'phenothiazines' describes the largest of the five main classes of 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. Use of phenothiazines has been associated with antiphospholipid syndrome, but no causal relationship has been established. 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). The synthetic dye methylene blue, containing the structure, was described in 1876. Many water-soluble phenothiazine derivatives, such as methylene blue, methylene green, thionine, and others, can be electropolymerized into conductive polymers used as electrocatalysts for NADH oxidation in enzymatic biosensors and biofuel cells. Phenothiazine is used as an anaerobic inhibitor for acrylic acid polymerization, often used as an in-process inhibitor during the purification of acrylic acid. 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, and Reconox.