Phenothiazine
Phenothiazine, also called dibenzothiazine or thiodiphenylamine is a yellow or green crystalline compound soluble in hot acetic acid, benzene, and ether. It is a three-ring structure compound in which two benzene rings are joined by a sulfur and nitrogen atom at nonadjacent positions. It is obtained by fusing diphenylamine with sulfur.
It is a dibenzo derivative of thiazine, although thiazine itself is not used as a starting point in the manufacturing of this molecule.
It is a semi-volatile organic compound and environmental toxicant of concern to the United States Environmental Protection Agency.[1]
Overview
The phenothiazine structure occurs in various neuroleptic drugs, e.g. Chlorpromazine. The synthetic dye methylene blue, containing the structure, was invented in 1876. Phenothiazine was introduced by DuPont as an insecticide in 1935.[2] It is sometimes used as an antihelminthic in livestock. It is used as an industrial chemical in the manufacture of rubber additives.[3]
Phenothiazine pesticides work by affecting the nervous system of insects, inhibiting the breakdown of acetylcholine by disabling the enzyme acetylcholinesterase. Many of the side effects of phenothiazine neuroleptic antipsychotics are due to their anticholinergic blocking effects.[4]
Phenothiazine is also a potent alpha-adrenergic blocking agent.
Synonyms for the chemical phenothiazine
Dibenzoparathiazine Thiodiphenylamine; AFI-Tiazin; Agrazine; Antiverm; Biverm; Dibenzothiazine; Orimon; Thiodiphenylamine; Lethelmin; Souframine; Nemazene; Vermitin; Padophene; Fenoverm; Fentiazine; Contaverm; Fenothiazine; [5]
Phenothiazine-derivative drugs
The term "phenothiazines" is used to describe 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.[6]
The phenothiazine class of neuroleptics are closely related to the thioxanthenes which are very similar pharmacologically.
There are three groups of phenothiazine antipsychotics, differing by their chemical structure and their pharmacological effects. They are the aliphatic compounds, the piperidines and piperazines. An aliphatic compound, piperidine or piperazine functional group is added to the phenothiazine molecule for the purpose of enhancing absorption and bioavailability of the phenothiazine chemical.
| Group | Autonomic | Example | Sedative | Extrapyramidal side-effect |
| Aliphatic compounds | ||||
| moderate | Chlorpromazine (marketed as Thorazine, Chlor-PZ, Klorazine, Promachlor, Promapar, Sonazine, Chlorprom, Chlor-Promanyl, Largactil) | strong | moderate | |
| Promazine (trade name Sparine) | moderate | moderate | ||
| Triflupromazine (trade names Stelazine, Clinazine, Novaflurazine, Pentazine, Terfluzine, Triflurin, Vesprin) | strong | moderate/strong | ||
| Levomepromazine in Germany and Methotrimeprazine in America (trade names Nozinan, Levoprome) | extremely strong | low | ||
| Piperidines | strong | Mesoridazine (trade name Serentil) | strong | weak |
| Thioridazine (trade names Mellaril, Novoridazine, Thioril) | strong | weak | ||
| Piperazines | weak | Fluphenazine (trade names Prolixin, Permitil, Modecate, Moditen) | weak/moderate | strong |
| Perphenazine (sold as Trilafon, Etrafon, Triavil, Phenazine) | weak/moderate | strong | ||
| Flupentixol (sold as Depixol, Fluanxol) | moderate | strong | ||
| Prochlorperazine (trade names Compazine, Stemetil) | ||||
| Trifluoperazine (trade name Stelazine) | moderate | strong |
References
- ^ Five-Year Review Report Forest Glen Mobile Home Subdivision Site City of Niagara Falls and Town of Niagara Niagara County, New York Prepared by U.S. Environmental Protection Agency September 2002
- ^ History of Insecticides and Control Equipment Clemson University Pesticide Information Program.
- ^ NPL Site Narrative for Forest Glen Mobile Home Subdivision FOREST GLEN MOBILE HOME SUBDIVISION Niagara Falls, New York Federal Register Notice: November 21, 1989
- ^ "Facts and Comparisons" III W. Port Plaza, Suite 300 St. Louis MO. USA 63146-3098 (telephone 314-216-2100 or 1-800-223-0554). The updatable section called "Antipsychotic Agents" is (c)1990
- ^ U.S. Department of Labor Occupational Safety & Health Administration Chemical Sampling Information Phenothiazine Also see: OSHA Also see:PAN Pesticides Database
- ^ Rang; Dale et al, Pharmacology, 6th edition
Further reading
- 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.