Phenothiazine

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Phenothiazine
Phenothiazine
Phenothiazine3D
IUPAC name 10H-phenothiazine
Other names thiodiphenylamine, dibenzothiazine
Identifiers
CAS number [92-84-2]
Properties
Molecular formula C12H9NS
Molar mass 199.2762 g/mol
Appearance yellow rhombic leaflets or

diamond-shaped plates
Density  ? g/cm3, solid at STP
Melting point

185 °C
Boiling point

371 °C
Solubility in other solvents water, petroleum ether, chloroform
Acidity (pKa) approx 23 in DMSO
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

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 benzo 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]

Contents

[edit] Overview

It is commonly used as an intermediate chemical in the manufacture of various antipsychotic neuroleptic psychotropic drugs. It originally was developed as a synthetic dye in 1883,[2] and it was introduced by DuPont as an insecticide in 1935.[3] It is sometimes used as an antihelminthic in livestock. It is used as an industrial chemical in the manufacture of rubber additives.[4]

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.[5]

Phenothiazine is also a potent alpha-adrenergic blocking agent.

[edit] Synonyms for the chemical phenothiazine

Dibenzoparathiazine; Thiodiphenylamine; AFI-Tiazin; Agrazine; Antiverm; Biverm; Dibenzothiazine; Orimon; Lethelmin; Souframine; Nemazene; Vermitin; Padophene; Fenoverm; Phenovarm; Fentiazine; Contaverm; Fenothiazine, Ieeno; ENT 38; Helmetina; Helmetine, Penthazine; XL-50; Wurm-thional; Fentiazin; Padophene; Phenegic; Phenovis; Phenoxur; Reconox, Phenergan, Protazine; Thiergan[6]

[edit] 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.[7]

The phenothiazine class of neuroleptic antipsychotic psychotropics 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


[edit] References

  1. ^ 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
  2. ^ Whitaker R (2004). "The case against antipsychotic drugs: a 50-year record of doing more harm than good". Med. Hypotheses 62 (1): 5-13. doi:10.1016/S0306-9877(03)00293-7. PMID 14728997. 
  3. ^ History of Insecticides and Control Equipment Clemson University Pesticide Information Program.
  4. ^ NPL Site Narrative for Forest Glen Mobile Home Subdivision FOREST GLEN MOBILE HOME SUBDIVISION Niagara Falls, New York Federal Register Notice: November 21, 1989
  5. ^ "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
  6. ^ U.S. Department of Labor Occupational Safety & Health Administration Chemical Sampling Information Phenothiazine Also see: OSHA Also see:PAN Pesticides Database
  7. ^ Rang; Dale et al, Pharmacology, 6th edition

[edit] Further reading