PROMAZINE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H20N2S
Molecular Weight	284.419
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCCN1C2=CC=CC=C2SC3=CC=CC=C13

InChI

InChIKey=ZGUGWUXLJSTTMA-UHFFFAOYSA-N

InChI=1S/C17H20N2S/c1-18(2)12-7-13-19-14-8-3-5-10-16(14)20-17-11-6-4-9-15(17)19/h3-6,8-11H,7,12-13H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C17H20N2S
Molecular Weight	284.419
Charge	0
Count

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

Description
Sources: https://www.drugs.com/uk/promazine-25mg-tablets-leaflet.html
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00420 | https://www.ncbi.nlm.nih.gov/pubmed/22793499 | https://www.ncbi.nlm.nih.gov/pubmed/2863832 | https://www.ncbi.nlm.nih.gov/pubmed/12084453

Promazine (Sparine) is a phenothiazine neuroleptic used for short-term management of moderate to severe psychomotor agitation and treatment of agitation and restlessness in the elderly. Promazine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Promazine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Promazine does not appear to block dopamine within the tuberoinfundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with promazine. Promazine is not approved for human use in the United States. It is available in the US for veterinary use under the names Promazine and Tranquazine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499	Antagonist 2849	2.5 µM [IC50]
Serotonin 2 (5-HT2) receptor 90 Target ID: CHEMBL2095200 Sources: https://books.google.ru/books?id=QsofyIjFCeYC&pg=PA548&lpg=PA548&dq=LEVOMEPROMAZINE++5-hydroxytryptamine+receptors&source=bl&ots=ALMCiE6y_d&sig=0aSnEx9jbVLo92LDWIgjdQWzSCE&hl=ru&sa=X&ved=0ahUKEwiP4ejw_4DQAhXBPxoKHUgbDTMQ6AEINjAD#v=onepage&q=LEVOMEPROMAZINE%20%205-hydroxytryptamine%20receptors&f=false	Antagonist 2849
Dopamine receptor 60 Target ID: CHEMBL2096905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6105219	Antagonist 2849	1.0 µM [IC50]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18635692	Antagonist 2849	7.0 null [pKi]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18635692	Antagonist 2849	7.9 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Psychomotor agitation 6 Sources: https://www.drugs.com/uk/promazine-25mg-tablets-leaflet.html	Primary		Approved 8583	THORAZINE Approved Use Unknown Launch Date 1957
Agitation and restlessness in the elderly 4 Sources: https://www.drugs.com/uk/promazine-25mg-tablets-leaflet.html	Primary		Approved 8583	THORAZINE Approved Use Unknown Launch Date 1957

C_max

Value	Dose	Co-administered	Analyte	Population
71.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2265236/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
137 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2265236/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
45.7 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7714731/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PROMAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
132.2 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7714731/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
613 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2265236/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
759 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2265236/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
558 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7714731/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1163 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7714731/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Analyte	Population
16% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2265236/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
17% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2265236/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
10.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7714731/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7714731/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	PROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28766806	unhealthy, 79 years Health Status: unhealthy Age Group: 79 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/28766806	Disc. AE: Drug eruption eczematous... AEs leading to discontinuation/dose reduction: Drug eruption eczematous (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/28766806
50 mg single, intravenous Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/13458245	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/13458245	Sources: https://pubmed.ncbi.nlm.nih.gov/13458245

AEs

AE	Significance	Dose	Population
Drug eruption eczematous	1 patient Disc. AE	50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28766806	unhealthy, 79 years Health Status: unhealthy Age Group: 79 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/28766806

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	CYP1A1 389 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C19 1119 CYP2E1 729	BCRP 101 MRP2 146

Drug as perpetrator

Target	Modality	Activity
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31640190/	weak [Ki 8.273 uM]
BCRP 985	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes
MRP2 625	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/ \| https://pubmed.ncbi.nlm.nih.gov/19702528/	yes
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8459	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8459
ChemicalBook	CB5875452	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5875452
ZINC	ZINC000000010402	http://zinc15.docking.org/substances/ZINC000000010402

PubMed

Title	Date	PubMed
[Acute psychoses caused by digitalis poisoning].	1991 Nov-Dec	1669614
Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase.	2002 Apr-Jun	12180262
Contribution of human cytochrome p-450 isoforms to the metabolism of the simplest phenothiazine neuroleptic promazine.	2003 Apr	12721102
Minimal myocardial damage after tricyclic neuroleptic overdose - a case report.	2003 Jan	12649773
An evaluation of protein assays for quantitative determination of drugs.	2003 Jul 31	12834962
Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers.	2003 Mar	12688423
Interaction of alcohol and drugs in fatal poisonings.	2003 May	12774892
Substitution and solvent effects on the photophysical properties of several series of 10-alkylated phenothiazine derivatives.	2005 Apr 21	16833671
Relation of postmortem blood alcohol and drug concentrations in fatal poisonings involving amitriptyline, propoxyphene and promazine.	2005 Aug	16138729
Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.	2005 Dec	16135699
Densitometric high performance thin-layer chromatography identification and quantitative analysis of psychotropic drugs.	2005 Jan-Feb	15759728
Application notes on the use of softer X-rays for anomalous powder diffraction.	2005 Jul	15968118
The in vitro activity of phenothiazines against Mycobacterium avium: potential of thioridazine for therapy of the co-infected AIDS patient.	2005 Jul-Aug	15999542
Acute brain syndrome as a consequence of the Cronkhite-Canada syndrome.	2005 Jun	16395849
Development and validation of a capillary electrophoresis method for the determination of phenothiazines in human urine in the low nanogram per milliliter concentration range using field-amplified sample injection.	2005 Jun	15924366
Stability of the tranquilizer drug propionylpromazine hydrochloride in formulated products.	2005 Jun	15668921
Gastrointestinal bleeding and massive liver damage in neuroleptic malignant syndrome.	2005 Sep	18360563
A kinetic study on the phenothiazine dependent oxidation of NADH by bovine ceruloplasmin.	2006 Feb	16502325
Inhibitory effect of antipsychotic drugs on the Con A- and LPS-induced proliferative activity of mouse splenocytes: a possible mechanism of action.	2006 Jun	16845229
Determination of phenothiazines in pharmaceutical formulations and human urine using capillary electrophoresis with chemiluminescence detection.	2006 Jun	16718647
Experimental design optimization of a sequential injection method for promazine assay in bulk and pharmaceutical formulations.	2007	18350124
Drug adverse events and drop-out risk: a clinical case.	2007	17317475
The photo comet assay--a fast screening assay for the determination of photogenotoxicity in vitro.	2007 Aug 15	17572134
Synthesis and antitubercular activity of quaternized promazine and promethazine derivatives.	2007 Mar 1	17188865
QTc and psychopharmacs: are there any differences between monotherapy and polytherapy.	2007 May 3	17477877
Neurosyphilis, malaria, and the discovery of antipsychotic agents.	2008	18803105
The psychotropic drug olanzapine (Zyprexa) increases the area of acid glycerophospholipid monolayers.	2008 Apr	18249059
Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections? Lack of efficacy of promazine on SARS-CoV replication in a mouse model.	2008 Aug	18423639
Detection of photogenotoxicity in skin and eye in rat with the photo comet assay.	2008 Feb	18264593
Energetics of binding and protein unfolding upon amphiphilic drug complexation with a globular protein in different aqueous media.	2008 Jun 1	18222070
[Application of liquid chromatography coupled with mass spectrometry (LC/MS) to determine antidepressants in blood samples].	2008 Oct-Dec	19441687
P-glycoprotein senses its substrates and the lateral membrane packing density: consequences for the catalytic cycle.	2008 Sep 23	18759452
Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.	2009 Jul 14	19597541

Patents

Sample Use Guides

In Vivo Use Guide

100-200 mg four times daily

Route of Administration: Oral

In Vitro Use Guide

African green monkey kidney cells (Vero 76) were used for activity evaluation. The cells were grown in minimal essential medium (MEM) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Hyclone Laboratories; Logan UT). For antiviral assays, the serum was reduced to 2% and 50 µg/ml gentamicin added to the medium. Promazine was tested at varying concentrations (four log10 or eight 1/2 log10 dilutions). Virus and compound were added in equal volumes to near-confluent cell monolayers in 96- well tissue culture plates. The multiplicity of infection ranged from 0.001 to 0.004 in order to produce viral cytopathic effects (CPE) for each strain of virus in 100% of the cells in the virus control wells within 3–4 days. The plates were incubated at 37 °C in a 5% CO2 atmosphere until the cells in the virus control wells showed complete viral CPE as observed by light microscopy. Each concentration of drug was assayed for virus inhibition in triplicate and for cytotoxicity in duplicate. Six wells per plate were set aside as uninfected, untreated cell controls and six wells per plate received virus only and represented controls for virus replication. Calpain inhibitor IV was included as positive control drugs

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:52:51 GMT 2025` Edited by `admin` on `Mon Mar 31 17:52:51 GMT 2025`
Record UNII	O9M39HTM5W
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

COMBELEN

Preferred Name

English

PROMAZINE

Official Name

English

Promazine [WHO-DD]

Common Name

English

promazine [INN]

Common Name

English

PROMAZINE [HSDB]

Common Name

English

NSC-31447

Code

English

PROMAZINE [VANDF]

Common Name

English

PROMAZINE [MI]

Common Name

English

3-(10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE

Systematic Name

English

PROMAZINE [MART.]

Common Name

English

CHLORPROMAZINE HYDROCHLORIDE IMPURITY C [EP IMPURITY]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N05AA03