WordNet
- a compound used primarily in veterinary medicine to rid farm animals of internal parasites (同)thiodiphenylamine
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/21 17:26:26」(JST)
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| Names | |
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| IUPAC name
10H-phenothiazine
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| Other names
thiodiphenylamine, dibenzothiazine, dibenzoparathiazine, 10H-dibenzo-[b,e]-1,4-thiazine, PTZ
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| Identifiers | |
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CAS Number
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92-84-2 Y |
| ChEBI | CHEBI:37931 N |
| ChEMBL | ChEMBL828 Y |
| ChemSpider | 21106365 Y |
| Jmol interactive 3D | Image |
| KEGG | D02601 Y |
| UNII | GS9EX7QNU6 Y |
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InChI
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SMILES
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| Properties | |
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Chemical formula
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C12H9NS |
| Molar mass | 199.27 g/mol |
| Appearance | greenish-yellow rhombic leaflets or diamond-shaped plates |
| Melting point | 185 °C (365 °F; 458 K) |
| Boiling point | 371 °C (700 °F; 644 K) |
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Solubility in water
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0.00051 g/L (20 °C)[1] |
| Solubility in other solvents | benzene, ether, petroleum ether, chloroform, hot acetic acid, ethanol (slightly), mineral oil (slightly) |
| Acidity (pKa) | approx 23 in DMSO |
| Hazards | |
| US health exposure limits (NIOSH): | |
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PEL (Permissible)
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none[2] |
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REL (Recommended)
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TWA 5 mg/m3 [skin] |
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IDLH (Immediate danger
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N.D.[2] |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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| N verify (what is YN ?) | |
| Infobox references | |
Phenothiazine abbreviated PTZ is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds.
It is used in chemical manufacturing as a stabilizer or inhibitor. It was used in the mid-20th century as an insecticide and antihelminthic for livestock and humans, but was superseded by other compounds.
Derivatives of phenothiazine discovered in the 1940s revolutionized the field of psychiatry and allergy treatment. The earliest derivative, methylene blue, was one of the first antimalarial drugs, and as of 2015 derivatives are under investigation as possible anti-infective drugs. It is a prototypical pharmaceutical lead structure in modern medicinal chemistry.
Contents
- 1 Use
- 2 Former uses
- 3 Synthesis
- 4 Derivatives
- 4.1 Phenothiazine-derived drugs
- 4.2 Nondrug applications
- 5 Trade Names
- 6 References
- 7 Further reading
Use
In the manufacture of monomers, phenothiazine is used as a chemical stabilizer or inhibitor to prolong storage and shelf life of products such as acryloyl chloride.[3][4]
Former uses
Phenothiazine was formerly used as an insecticide and as a drug to treat infections with parasitic worms (antihelminthic) in livestock and people, but its use for those purposes has been superseded by other chemicals.
Phenothiazine was introduced by DuPont as an insecticide in 1935.[5] About 3,500,000 pounds were sold in the US in 1944.[6] However, because it was degraded by sunlight and air, it was difficult to determine how much to use in the field, and its use waned in the 1940s with the arrival of new pesticides like DDT that were more durable.[7]:161–162 As of July 2015 it is not registered for pesticide use in the US,[8] nor Europe, [4] nor Australia.[9]
It was introduced as antihelminthic in livestock in 1940 and is considered, with thiabendazole, to be the first modern antihelminthic.[10] The first instances of resistant were noted in 1961.[10] Uses for this purpose in the US are still described[11] but it has "virtually disappeared from the market."[12]:369
In the 1940s it also was introduced as antihelminthic for humans; since it was often given to children, the drug was often sold in chocolate, leading to the popular name, "worm chocolate." Phenothiazine was superseded by other drugs in the 1950s.[13]
Synthesis
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 diphenyl sulfides. Some of the pharmaceutically significant derivatives of phenothiazine are not prepared directly from phenothiazine,[14] although some of them are.[15]
Derivatives
Phenothiazine itself was a pioneering compound, but its derivatives revolutionized psychiatry and other fields of medicine. Other derivatives have been studied for possible use in advanced batteries and fuel cells.[13]
Phenothiazine-derived drugs
Methylene blue is technically a derivative of phenothiazine but was synthesized first; it was made in 1876 by Heinrich Caro at BASF and the structure was determined in 1885 by Heinrich August Bernthsen. Bernthsen synthesized phenothiazine in 1883.[13]
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 won a Nobel Prize based in part of that work. He became particularly interested in its use to stain bacteria, which he pursued into other organisms like Plasmodiidae – which 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.[13]
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.[13] 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.[13] The systematic research conducted by chemists to explore phenothiazine derivatives and their activity using was a pioneering example of medicinal chemistry; phenothiazine is often discussed as a prototypical example of a pharmaceutical lead structure.[13][16]
Today, 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.[13] Use of phenothiazines has been associated with antiphospholipid syndrome, but no causal relationship has been established.[17]
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).[16]
| Group | Autonomic | Example | Sedative | Extrapyramidal side effects |
| Aliphatic compounds | ||||
| moderate | Chlorpromazine (marketed as Thorazine, Aminazine, Chlor-PZ, Klorazine, Promachlor, Promapar, Sonazine, Chlorprom, Chlor-Promanyl, Largactil) | strong | moderate | |
| Promazine (trade name Sparine, Propazine) | moderate | moderate | ||
| Triflupromazine (trade names Clinazine, Novaflurazine, Pentazine, Terfluzine, Triflurin, Vesprin) | strong | moderate/strong | ||
| Levomepromazine in Germany, Russia and methotrimeprazine in America (trade names Nozinan, Levoprome, Tisercin) | extremely strong | low | ||
| Piperidines | strong | Mesoridazine (trade name Serentil) | strong | weak |
| Thioridazine (trade names Mellaril, Novoridazine, Thioril, Sonapax) | strong | weak | ||
| Piperazines | weak | Fluphenazine (trade names Prolixin, Permitil, Modecate, Moditen) | weak/moderate | strong |
| Perphenazine (sold as Trilafon, Etrafon, Triavil, Phenazine, Etaperazin) | weak/moderate | strong | ||
| Prochlorperazine (trade names Compazine, Stemetil) | ||||
| Trifluoperazine (trade name Stelazine, Triphtazine) | moderate | strong |
Flutiazin is a NSAID.
Nondrug applications
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.[18][19][20]
Trade Names
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.[21][22][23]
References
- ^ Sigma-Aldrich catalog
- ^ a b "NIOSH Pocket Guide to Chemical Hazards #0494". National Institute for Occupational Safety and Health (NIOSH).
- ^ PTZ Technical Information Bulletin Cytec PTZ Technical Information Bulletin
- ^ a b ECHA phenothiazine at the European Chemicals Authority Page accessed July 26, 2015. Note - Registered uses are only in manufacturing.
- ^ History of Insecticides and Control Equipment Clemson University Pesticide Information Program.
- ^ Robert Lee Metcalf. The Mode of Action of Organic Insecticides, Issues 1-5. National Academies, 1948, page 44
- ^ G. Matolcsy, M. Nádasy, V. Andriska. Studies in Environmental Science: Pesticide Chemistry. Elsevier, 1989 ISBN 9780080874913
- ^ Phenothiazine in the PAN Pesticides Database Page accessed July 26, 2015
- ^ Australian Pesticides and Veterinary Medicine Authority Phenothiazine Chemical Review Page accessed July 26, 2015
- ^ a b Nielsen MK, et al. Anthelmintic resistance in equine parasites--current evidence and knowledge gaps. Vet Parasitol. 2014 Jul 30;204(1-2):55-63. Review. PMID 24433852
- ^ The Texas A&M University System; Texas AgriLife Extension Service Integrated pest management of �flies in Texas dairies
- ^ Heinz Mehlhorn, Philip M. Armstrong. Encyclopedic Reference of Parasitology: Diseases, Treatment, Therapy, Volume 2. Springer Science & Business Media, 2001 ISBN 9783540668299
- ^ a b c d e f g h Ohlow MJ, Moosmann B. Phenothiazine: the seven lives of pharmacology's first lead structure. Drug Discov Today. 2011 Feb;16(3-4):119-31. PMID 21237283
- ^ Gérard Taurand, "Phenothiazine and Derivatives" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.doi:10.1002/14356007.a19_387
- ^ T. Kahl, K.-W. Schröder, F. R. Lawrence, W. J. Marshall, Hartmut Höke, Rudolf Jäckh, "Aniline" in Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH: Weinheim.
- ^ a b Jaszczyszyn A, et al. Chemical structure of phenothiazines and their biological activity. Pharmacol Rep. 2012;64(1):16-23. Review. PMID 22580516
- ^ "Antiphospholipid Syndrome - Doctor's Information | Patient". Patient. Retrieved 2015-07-25.
- ^ "Electrocatalytic oxidation of reduced nicotinamide coenzymes at Methylene Green-modified electrodes and fabrication of amperometric alcohol biosensors". Analytica Chimica Acta 285: 125–133. doi:10.1016/0003-2670(94)85016-X.
- ^ "Electropolymerized Azines: Part II. In a Search of the Best Electrocatalyst of NADH Oxidation". Electroanalysis 11: 553–557. doi:10.1002/(SICI)1521-4109(199906)11:8<553::AID-ELAN553>3.0.CO;2-6.
- ^ "Citric acid cycle biomimic on a carbon electrode". Biosensors and Bioelectronics 24: 939–944. doi:10.1016/j.bios.2008.07.043.
- ^ U.S. Department of Labor Occupational Safety & Health Administration Chemical Sampling Information Phenothiazine
- ^ OSHA
- ^ PAN Pesticides Database
Further reading
- MSDS
- 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.
- CDC - NIOSH Pocket Guide to Chemical Hazards
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UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. 制吐剤の特性 characteristics of antiemetic drugs
- 2. 第1世代抗精神病剤：薬理学、投与、および副作用の比較 first generation antipsychotic medications pharmacology administration and comparative side effects
- 3. 第一世代（定型）抗精神病剤中毒 first generation typical antipsychotic medication poisoning
- 4. ソラレン・紫外線A（PUVA）光化学療法 psoralen plus ultraviolet a puva photochemotherapy
- 5. 思春期および成人における労作性熱中症：疫学、体温調節、危険因子、および診断 exertional heat illness in adolescents and adults epidemiology thermoregulation risk factors and diagnosis
English Journal
- Synthesis and properties of new low band gap semiconducting polymers.
- Kim JH, Kang J, Mi D, Xu F, Jin SH, Chun HH, Hwang DH.
- Journal of nanoscience and nanotechnology.J Nanosci Nanotechnol.2014 Jul;14(7):5187-91.
- Low band gap organic semiconducting polymers were prepared as p-type donors for organic photovoltaic devices. A novel dibrominated monomer composed of phenothiazine, thiophene, and benzothiadiazole (DPDTBT) was synthesized as a low band gap core block. DPDTBT was copolymerized with three different b
- PMID 24758000
- Trifluoperazine rescues human dopaminergic cells from wild-type α-synuclein-induced toxicity.
- Höllerhage M1, Goebel JN2, de Andrade A3, Hildebrandt T4, Dolga A5, Culmsee C5, Oertel WH2, Hengerer B6, Höglinger GU7.
- Neurobiology of aging.Neurobiol Aging.2014 Jul;35(7):1700-11. doi: 10.1016/j.neurobiolaging.2014.01.027. Epub 2014 Jan 28.
- Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder. Presently, there is no causal therapy available to slow down or halt disease progression. The presynaptic protein alpha-synuclein aggregates to form intraneuronal Lewy bodies in PD. It is generally believed that inter
- PMID 24559643
- Broad specific enzyme-linked immunosorbent assay for determination of residual phenothiazine drugs in swine tissues.
- Gao BL1, Liu J1, Dong LX2, Zhang L1, Qin JH1, Wang JP3.
- Analytical biochemistry.Anal Biochem.2014 Jun 1;454:7-13. doi: 10.1016/j.ab.2014.02.032. Epub 2014 Mar 11.
- In this study, a novel generic hapten of phenothiazine drugs was synthesized by derivatization of 2-chlorophenothiazine with sodium bromoacetate. Then the hapten was coupled to bovine serum albumin for production of the monoclonal antibody. Results showed that the obtained monoclonal antibody recogn
- PMID 24631517
Japanese Journal
- Aggregation control of organic sensitizers for panchromatic dye co-sensitized solar cells
- Lee Chi,Kim Sang,Jung Mi,Ahn Kwang-Soon,Han Yoon,Kim Jae
- Jpn. J. Appl. Phys. 53(8S3), 08NC04, 2014-07-24
- … Co-sensitized TiO<inf>2</inf>photo-electrodes were prepared from a phenothiazine chromophore for the RED dye and a squaraine chromophore for the BLUE dye to achieve panchromatic light absorption in dye co-sensitized solar cells (DSSCs). …
- NAID 150000109604
- 私の研究人生；シナプス信号伝達から行動へ
- 黒見 坦
- 薬学雑誌. 乙号 134(8), 851-866, 2014
- … 1) Electrophysiological experiments in cats and rabbits suggested that a new type of analgesic, the phenothiazine derivative levomepromazine, exerts analgesic effects by depressing emotional responses accompanying the sensation of pain. …
- NAID 130004677651
- Quantification of Antioxidants by Using Chlorpromazine Hydrochloride: Application of the Method to Food and Medicinal Plant Samples
- NAGARAJA Padmarajaiah,ARADHANA Narayanan,SUMA Aandamurthy,SHIVAKUMAR Anantharaman,CHAMARAJA Nelligere Arkeshwaraiah
- Analytical Sciences 30(2), 251-256, 2014
- … Chlorpromazine hydrochloride (CPH) (3-(2-chloro-phenothiazine-10-yl)-propyl] dimethylamine hydrochloride) has been the subject of a large number of studies employing a broad spectrum of oxidants, and chosen to examine the course of electron transfer reactions. …
- NAID 130004442261
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★リンクテーブル★
| リンク元 | 「フェノチアジン」「フェノチアジン誘導体」「フェノサイアジン」 |
| 拡張検索 | 「phenothiazine poisoning」「phenothiazine derivative」 |
| 関連記事 | 「phenothiazines」 |
「フェノチアジン」
概念
- 主として強い鎮静、睡眠作用を必要とする場合に使う
- ムスカリン性アセチルコリン受容体遮断作用が強いので、錐体外路症状は少ない。
- 末梢性コリン作用による副作用が生じやすい
- アドレナリンα1受容体を遮断するため鎮静、催眠作用が強く、興奮や不眠を示す患者によい。
作用機序
| 伝達物質 | 局在 | |
| A15 | ドーパミン | 嗅球の糸球体周囲細胞 |
| A14 | 視床下部前部 | |
| A13 | 不確帯 | |
| A12 | 弓状核(漏斗核) | |
| A11 | 視床下部後部 | |
| A10 | 中脳腹側被蓋野 | |
| A9 | 黒質緻密部 | |
| A8 | 赤核後核 |
薬理作用
「フェノチアジン誘導体」
- フェノチアジン核/骨格を有する化合物
作用機序
- D2受容体拮抗
適応
- 抗精神病薬：統合失調症、躁病
副作用
- 錐体外路症状、意識障害、血圧低下(自律神経遮断作用による？)
所属する薬物
- 抗精神病薬
「フェノサイアジン」
- 英
- phenothiazine
- 関
- フェノチアジン、フェノチアジン系、フェノチアジン系化合物