Phenothiazine

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H9NS
Molecular Weight	199.272
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N1C2=CC=CC=C2SC3=CC=CC=C13

InChI

InChIKey=WJFKNYWRSNBZNX-UHFFFAOYSA-N

InChI=1S/C12H9NS/c1-3-7-11-9(5-1)13-10-6-2-4-8-12(10)14-11/h1-8,13H

HIDE SMILES / InChI

Molecular Formula	C12H9NS
Molecular Weight	199.272
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12371440 | https://www.ncbi.nlm.nih.gov/pubmed/7047129 | https://www.ncbi.nlm.nih.gov/pubmed/5328491 | https://www.ncbi.nlm.nih.gov/pubmed/16772768

Phenothiazine, the parent compound of a multitude of present-day drugs, has been employed on an extensive scale for its insecticidal, fungicidal, antibacterial and anthelmintic properties. Phenothiazine was formerly used as an insecticide and as a drug to treat infections with parasitic worms (antihelminthic) in livestock and people. It was introduced as antihelminthic in livestock in 1940 and is considered, with thiabendazole, to be the first modern antihelminthic. Almost a catholicon, its widespread use in animals and man has led to the uncovering of many adverse reactions encompassing effects on blood elements, neuromuscular problems and photosensitization. Its potential side effects have now limited its use. The chemical structure of phenothiazine provides a most valuable molecular template for the development of agents able to interact with a wide variety of biological processes. Synthetic phenothiazines (with aliphatic, methylpiperazine, piperazine-ethanol, piperazine-ethyl, or piperidine side-chain) and/or phenothiazine-derived agents e.g., thioxanthenes, benzepines, imonostilbenes, tricyclic antidepressants, dimetothiazine, and cyproheptadine have been effective in the treatment of a number of medical conditions with widely different etiology. These include various currently clinically used drugs for their significant antihistamic, antipsychotic, anticholinergic (antiparkinson), antipruritic, and/or antiemetic properties.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 311 Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2874041	Antagonist 2849
Trichostrongylus colubriformis 1 Target ID: CHEMBL613454 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7255907	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Helminthiasis 39 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8498743 https://www.ncbi.nlm.nih.gov/pubmed/14952386 https://www.ncbi.nlm.nih.gov/pubmed/3284172 https://www.ncbi.nlm.nih.gov/pubmed/6543053 https://www.ncbi.nlm.nih.gov/pubmed/7255907	Curative		Approved 8583	Helmetina Approved Use Helminthiasis

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429 CYP2A6 879 P-gp 1741 CYP1A2 2153 CYP2E1 1060 CYP2C19 2057 BCRP 910	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMODI4In19	inconclusive [IC50 31.6228 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 40.0	no [IC50 14.9601 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDgyOCJ9fQ==	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDgyOCJ9fQ==	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDgyOCJ9fQ==	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMODI4In19	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDgyOCJ9fQ==	no [IC50 >10 uM]
BCRP 985	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 110.0	no
MRP1 232	activator 342 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 84.0	no
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 112.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 18.0	yes [EC50 0.7079 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDgyOCJ9fQ==	yes [IC50 0.016 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 519 \| 530	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/7108#section=Biological-Test-Results Page: 27.0

PubMed

Title	Date	PubMed
[Photosensitivity induced skin diseases].	2001	11828854
A case series of drug-induced long QT syndrome and Torsade de Pointes.	2001 Dec	11989578
Protective activity of aromatic amines and imines against oxidative nerve cell death.	2001 Nov	11767950
Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans.	2001 Nov	11765142
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.	2001 Nov-Dec	11985335
A TLC visualisation reagent for dimethylamphetamine and other abused tertiary amines.	2001 Oct-Dec	11793881
[The role of L-ascorbic acid in free radical reactions].	2002	12587430
Insomnia in children: when are hypnotics indicated?	2002	12038875
Perazine for schizophrenia.	2002	11869638
In vitro photodynamic activity of a series of methylene blue analogues.	2002 Apr	12003129
Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase.	2002 Apr-Jun	12180262
[Reversible cardiomyopathy induced by psychotropic drugs: case report and literature overview].	2002 Dec	12608134
Synthesis and characterization of pi-stacked phenothiazine-labeled oligodeoxynucleotides.	2002 Dec 26	12489932
Spectrophotometric determination of cerium(IV) using a phenothiazine derivative.	2002 Feb	11874120
Underlying endotoxemia augments toxic responses to chlorpromazine: is there a relationship to drug idiosyncrasy?	2002 Feb	11805205
Palladium-catalyzed stereocontrolled vinylation of azoles and phenothiazine.	2002 Feb 21	11843607
Excited-state properties and in vitro phototoxicity studies of three phenothiazine derivatives.	2002 Jan	11837323
Virus inactivation in blood components by photoactive phenothiazine dyes.	2002 Jan	11788930
A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache.	2002 Jan	11781912
Synthesis and characterization of phenothiazine labeled oligodeoxynucleotides: novel 2'-deoxyadenosine and thymidine probes for labeling DNA.	2002 Jan-Feb	11792181
Low concentrations of chlorpromazine and related phenothiazines stimulate gene transfer in HeLa cells via receptor-mediated endocytosis.	2002 Jan-Mar	11839208
Antimicrobial potentiality of a phenothiazine group of antipsychotic drug-prochlorperazine.	2002 Jul	12597553
Purification method for recombinant proteins based on a fusion between the target protein and the C-terminus of calmodulin.	2002 Jul	12172685
Benzo[b]-1,8-naphthyridine derivatives: synthesis and reversal activity on multidrug resistance.	2002 Jul-Aug	12174889
Inhibition of butyrylcholinesterase by phenothiazine derivatives.	2002 Jun	12443046
Partition of N-monodemethylated phenothiazine drugs to phosphatidylcholine bilayer vesicles studied by second-derivative spectrophotometry.	2002 Jun	12115855
Clozapine use and risk of diabetes mellitus.	2002 Jun	12006892
Stability indicating methods for assay of mequitazine in presence of its degradate.	2002 Jun 20	12062671
Design, synthesis, and evaluation of new chemosensitizers in multi-drug-resistant Plasmodium falciparum.	2002 Jun 20	12061877
Novel phenothiazine antimalarials: synthesis, antimalarial activity, and inhibition of the formation of beta-haematin.	2002 Mar 1	11911834
Quantification of perphenazine in eurasian otter (Lutra lutra lutra) urine samples by gas chromatography-mass spectrometry.	2002 Mar 25	11936697
Interaction of protonated anticancer thiazines with water-insoluble phospholipids and antineoplastic agents.	2002 Mar-Apr	12014679
Thioridazine interacts with the membrane of mitochondria acquiring antioxidant activity toward apoptosis--potentially implicated mechanisms.	2002 May	11976278
[Hepatic tolerance of atypical antipsychotic drugs].	2002 Nov-Dec	12506267
Class-selective drug detection: fluorescently-labeled calmodulin as the biorecognition element for phenothiazines and tricyclic antidepressants.	2002 Nov-Dec	12440852
In vitro chloroquine resistance modulation study on fresh isolates of Brazilian Plasmodium falciparum: intrinsic antimalarial activity of phenothiazine drugs.	2002 Oct	12471433
Chlorpromazine oxidation by hydroperoxidase activity of covalent immobilized lipoxygenase.	2002 Oct	12241550
Protometric thermometric titrations of sparingly soluble compounds in water in the presence of n-octanol.	2002 Oct 15	12367687
Fate of the anthelmintic, phenothiazine, in man.	2002 Sep	12396274
Inhibition of P-glycoprotein transport function by N-acylphenothiazines.	2002 Sep-Oct	12530010
Antiepileptic-antipsychotic drug interactions: a critical review of the evidence.	2002 Sep-Oct	12410063
Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures.	2002 Sep-Oct	12387489
Trifluoperazine effects on anionic and zwitterionic micelles: a study by small angle X-ray scattering.	2003 Apr 15	12686194
Inactivation of pathogens in platelet concentrates by using a two-step procedure.	2003 Feb	12609015
Electrical communication between glucose oxidase and electrodes mediated by phenothiazine-labeled poly(ethylene oxide) bonded to lysine residues on the enzyme surface.	2003 Feb 15	12622383
Lipids as a target for drugs modulating multidrug resistance of cancer cells.	2003 Jan	12528987
In vitro human plasma leucine(5)-enkephalin degradation is inhibited by a select number of drugs with the phenothiazine molecule in their chemical structure.	2003 Jan	12444298
Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers.	2003 Mar	12688423
Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea.	2003 Mar	12639046
Amperometric determination of choline released from rat submandibular gland acinar cells using a choline oxidase biosensor.	2003 Mar	12485764

Patents

Sample Use Guides

In Vivo Use Guide

Man: 6 mg/kg body wt

Route of Administration: Oral

In Vitro Use Guide

Phenothiazines mostly substitutes at position 10 with the dialkylaminoalkyl groups and additionally at position 2 with small groups exhibit valuable activities such as neuroleptic, antiemetic, antihistaminic, antipuritic, analgesic and antihelmintic. 2-trifluoromethyl-10-(4-aminobutyl)phenothiazine inhibits S. cerevisiae strains and T. mentagrophites with MIC of 0.4 ug/mL and 1.5 ug/mL, respectively. 10-carbamoylalkylphenothiazines shows significant activities against Gram-positive Bacillus subtilis with MIC’s in the range of 7.8 ug/mL–30 ug/mL.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:55:15 GMT 2025` Edited by `admin` on `Mon Mar 31 17:55:15 GMT 2025`
Record UNII	GS9EX7QNU6
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Phenothiazine

Official Name

English

ENT-38

Preferred Name

English

PHENOTHIAZINE [GREEN BOOK]

Common Name

English

ALIMEMAZINE HEMITARTRATE IMPURITY C [EP IMPURITY]

Common Name

English

10H-PHENOTHIAZINE

Common Name

English

CONTAVERM

Common Name

English

PROMETHAZINE HYDROCHLORIDE IMPURITY A [EP IMPURITY]

Common Name

English

DANIKOROPA

Common Name

English

PHENOTHIAZINE [USP-RS]

Common Name

English

PHENOTHIAZINE [MI]

Common Name

English

FENOVERM

Common Name

English

PHENOTHIAZINE [HSDB]

Common Name

English

NSC-2037

Code

English

phenothiazine [INN]

Common Name

English

Phenothiazine [WHO-DD]

Common Name

English

THIODIPHENYLAMINE

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 520.1802c