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=C(SC3=C1C=CC=C3)C=CC=C2

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

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 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499	Antagonist 2778	2.5 µM [IC50]
Serotonin 2 (5-HT2) receptor 87 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 2778
Dopamine receptor 60 Target ID: CHEMBL2096905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6105219	Antagonist 2778	1.0 µM [IC50]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18635692	Antagonist 2778	7.0 null [pKi]
Serotonin 2a (5-HT2a) receptor 231 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18635692	Antagonist 2778	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 8429	THORAZINE Approved Use Unknown Launch Date -3.82319985E11
Agitation and restlessness in the elderly 4 Sources: https://www.drugs.com/uk/promazine-25mg-tablets-leaflet.html	Primary		Approved 8429	THORAZINE Approved Use Unknown Launch Date -3.82319985E11

C_max

Value	Dose	Analyte	Population
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
25 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9869384/	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: UNKNOWN
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Analyte	Population
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
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
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
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

F_unbound

Value	Dose	Analyte	Population
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
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
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
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

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 n = 1 Health Status: unhealthy Condition: Alzheimer’s disease Age Group: 79 years Sex: M Population Size: 1 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 n = 16 Health Status: unhealthy Population Size: 16 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 n = 1 Health Status: unhealthy Condition: Alzheimer’s disease Age Group: 79 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28766806

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C19 991 CYP2E1 667	BCRP 75 MRP2 111

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31640190/	weak [Ki 8.273 uM]
BCRP 773	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes
MRP2 475	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/ \| https://pubmed.ncbi.nlm.nih.gov/19702528/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP3A4 1737	substrate 3367 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 normovolemic hemodilution (ANH). Der Anaesthesist (2000) 49: 939-948].	2001 Aug	11556172
Use of laccase together with redox mediators to decolourize Remazol Brilliant Blue R.	2001 Aug 23	11500205
A liquid chromatographic method for the simultaneous determination of promethazine and three of its metabolites in plasma using electrochemical and UV detectors.	2001 Feb	11245229
[Inactivation of Trypanosoma cruzi trypanothione reductase by phenothiazine cationic free radicals].	2001 Jan-Mar	11407019
Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping.	2001 Oct	11606321
Fructose-1,6-diphosphate attenuates acute lung injury induced by ischemia-reperfusion in rats.	2002 Jul	12130986
Partition of N-monodemethylated phenothiazine drugs to phosphatidylcholine bilayer vesicles studied by second-derivative spectrophotometry.	2002 Jun	12115855
Conventional and atypical antipsychotics in the elderly : a review.	2003	17535043
[Neuroleptic malignant syndrome].	2003	14569909
Minimal myocardial damage after tricyclic neuroleptic overdose - a case report.	2003 Jan	12649773
Inhibition of rat liver CYP2D in vitro and after 1-day and long-term exposure to neuroleptics in vivo-possible involvement of different mechanisms.	2005 Jan	15572279
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
Direct effects of neuroleptics on the activity of CYP2A in the liver of rats.	2005 Nov-Dec	16382210
A kinetic study on the phenothiazine dependent oxidation of NADH by bovine ceruloplasmin.	2006 Feb	16502325
Interactions of recombinant prions with compounds of therapeutical significance.	2006 Jun 2	16630566
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
Thermodynamic studies of drug-alpha-cyclodextrin interactions in water at 298.15 K: promazine hydrochloride/chlorpromazine hydrochloride + alpha-cyclodextrin + H(2)O systems.	2007 Dec 6	17988113
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
Determination of selected phenothiazines in human plasma by solid-phase extraction and liquid chromatography with coulometric detection.	2008 Aug 29	18706338
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
[Drug-induced agranulocytosis--case reports and literature review].	2009	19788146
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009 Dec 2	19956587
Simultaneous chemiluminescence determination of promazine and fluphenazine using support vector regression.	2009 Jul 15	19559917

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

Name

Type

Language

PROMAZINE

Official Name

English

COMBELEN

Brand 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