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
Trifluoperazine effects on anionic and zwitterionic micelles: a study by small angle X-ray scattering.	2003-04-15	12686194
Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers.	2003-03	12688423
Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea.	2003-03	12639046
Amperometric determination of choline released from rat submandibular gland acinar cells using a choline oxidase biosensor.	2003-03	12485764
Electrical communication between glucose oxidase and electrodes mediated by phenothiazine-labeled poly(ethylene oxide) bonded to lysine residues on the enzyme surface.	2003-02-15	12622383
Inactivation of pathogens in platelet concentrates by using a two-step procedure.	2003-02	12609015
Inhibition of P-glycoprotein transport function by N-acylphenothiazines.	2003-01-18	12530010
Lipids as a target for drugs modulating multidrug resistance of cancer cells.	2003-01	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.	2003-01	12444298
[Hepatic tolerance of atypical antipsychotic drugs].	2002-12-31	12506267
Synthesis and characterization of pi-stacked phenothiazine-labeled oligodeoxynucleotides.	2002-12-26	12489932
[Reversible cardiomyopathy induced by psychotropic drugs: case report and literature overview].	2002-12	12608134
Class-selective drug detection: fluorescently-labeled calmodulin as the biorecognition element for phenothiazines and tricyclic antidepressants.	2002-11-21	12440852
Antiepileptic-antipsychotic drug interactions: a critical review of the evidence.	2002-11-01	12410063
Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures.	2002-10-22	12387489
Protometric thermometric titrations of sparingly soluble compounds in water in the presence of n-octanol.	2002-10-15	12367687
In vitro chloroquine resistance modulation study on fresh isolates of Brazilian Plasmodium falciparum: intrinsic antimalarial activity of phenothiazine drugs.	2002-10	12471433
Chlorpromazine oxidation by hydroperoxidase activity of covalent immobilized lipoxygenase.	2002-10	12241550
The contribution of cytochrome P-450 isoenzymes to the metabolism of phenothiazine neuroleptics.	2002-10	12208554
Platelet serotonin transporter in schizophrenic patients with and without neuroleptic treatment.	2002-10	12106771
Cataract occurrence with antipsychotic drugs.	2002-09-26	12297603
Fate of the anthelmintic, phenothiazine, in man.	2002-09	12396274
Gravimetric and spectrophotometric determination of some phenothiazine and imidazole derivatives in coated tablets and tablets.	2002-08-29	12197611
A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma.	2002-08-27	12189542
Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase.	2002-08-16	12180262
Benzo[b]-1,8-naphthyridine derivatives: synthesis and reversal activity on multidrug resistance.	2002-08-15	12174889
Mechanism of the oxidation of sulfides by dioxiranes. 1. Intermediacy of a 10-S-4 hypervalent sulfur adduct.	2002-08-07	12149020
The alterations of lipid bilayer fluidity induced by newly synthesized phenothiazine derivative.	2002-08-02	12128180
Drug-associated heat stroke.	2002-08	12190212
Photodriven electron and energy transfer from a light-harvesting metallodendrimer.	2002-07-01	12079481
Antimicrobial potentiality of a phenothiazine group of antipsychotic drug-prochlorperazine.	2002-07	12597553
Purification method for recombinant proteins based on a fusion between the target protein and the C-terminus of calmodulin.	2002-07	12172685
Simultaneous determination of promethazine, chlorpromazine, and perphenazine by multivariate calibration methods and derivative spectrophotometry.	2002-06-27	12083247
Stability indicating methods for assay of mequitazine in presence of its degradate.	2002-06-20	12062671
Design, synthesis, and evaluation of new chemosensitizers in multi-drug-resistant Plasmodium falciparum.	2002-06-20	12061877
Inhibition of butyrylcholinesterase by phenothiazine derivatives.	2002-06	12443046
Partition of N-monodemethylated phenothiazine drugs to phosphatidylcholine bilayer vesicles studied by second-derivative spectrophotometry.	2002-06	12115855
Clozapine use and risk of diabetes mellitus.	2002-06	12006892
Investigation of interaction of promethazine with cyclodextrins.	2002-05-25	12026112
Interaction of protonated anticancer thiazines with water-insoluble phospholipids and antineoplastic agents.	2002-05-17	12014679
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.	2002-05-03	11985335
Thioridazine interacts with the membrane of mitochondria acquiring antioxidant activity toward apoptosis--potentially implicated mechanisms.	2002-05	11976278
In vitro photodynamic activity of a series of methylene blue analogues.	2002-04	12003129
Effects of atypical antipsychotics on vertebrate neuromuscular transmission.	2002-04	11985825
Mimicking dye-based functions of natural blue-light photoreceptors by studying photoinduced energy and electron transfer in a pyrene-isoalloxazine(flavin)-phenothiazine triad.	2002-03-07	12120541
[The role of L-ascorbic acid in free radical reactions].	2002	12587430
A new phenothiazine derivative alters the fluidity and thermotropic behaviour of phosphatidylcholine model membranes.	2002	12097973
Spectrophotometric determination of the phosphatidylcholine liposomes/water partition coefficients and the protonation equilibrium constants of phenothiazine derivatives.	2002	12097965
Insomnia in children: when are hypnotics indicated?	2002	12038875
A case series of drug-induced long QT syndrome and Torsade de Pointes.	2001-12	11989578

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