PROMAZINE

US Previously Marketed

First approved in 1956

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 313 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499	Antagonist 2760	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 2760
Dopamine receptor 58 Target ID: CHEMBL2096905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6105219	Antagonist 2760	1.0 µM [IC50]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18635692	Antagonist 2760	7.0 null [pKi]
Serotonin 2a (5-HT2a) receptor 230 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18635692	Antagonist 2760	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 8360	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 8360	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 1709	substrate 1010	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437	CYP1A1 348 CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C19 985 CYP2E1 648	BCRP 75 MRP2 111

Drug as perpetrator

Target	Modality	Activity
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/31640190/	weak [Ki 8.273 uM]
BCRP 765	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes
MRP2 459	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/ \| https://pubmed.ncbi.nlm.nih.gov/19702528/	yes
CYP2B6 660	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12721102/	yes
CYP3A4 1709	substrate 3326 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
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
Examination of iron (III) and hexacyanoferrate (III) ions as reagents for the spectrophotometric determination of promazine and perazine.	2001 Nov-Dec	12197613
Fructose-1,6-diphosphate attenuates acute lung injury induced by ischemia-reperfusion in rats.	2002 Jul	12130986
Conventional and atypical antipsychotics in the elderly : a review.	2003	17535043
[Neuroleptic malignant syndrome].	2003	14569909
Contribution of human cytochrome p-450 isoforms to the metabolism of the simplest phenothiazine neuroleptic promazine.	2003 Apr	12721102
Interaction of alcohol and drugs in fatal poisonings.	2003 May	12774892
CSM thioridazine advice.	2004 Aug	15296567
Peroxidase catalysed formation of cytotoxic prooxidant phenothiazine free radicals at physiological pH.	2004 Dec 30	15607761
Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs.	2004 May 15	15110833
Halogenation of drugs enhances membrane binding and permeation.	2004 May 3	15122640
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
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
Interactions between neuroleptics and CYP2C6 in rat liver--in vitro and ex vivo study.	2005 Nov-Dec	16382211
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
Interactions of recombinant prions with compounds of therapeutical significance.	2006 Jun 2	16630566
Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study.	2006 May 24	16723019
Use of a fluorescent polarization based high throughput assay to identify new calmodulin ligands.	2006 Nov	17081635
Trypanosoma cruzi dihydrolipoamide dehydrogenase as target for phenothiazine cationic radicals. Effect of antioxidants.	2006 Sep	17017892
The photo comet assay--a fast screening assay for the determination of photogenotoxicity in vitro.	2007 Aug 15	17572134
Modification of the thermal unfolding pathways of myoglobin upon drug interaction in different aqueous media.	2007 Dec 13	18020438
Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities: case report.	2007 Dec 20	18096026
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
Inflammation-related genes up-regulated in schizophrenia brains.	2007 Sep 6	17822540
The activity of cytochrome P450 CYP2B in rat liver during neuroleptic treatment.	2007 Sep-Oct	18048963
Neurosyphilis, malaria, and the discovery of antipsychotic agents.	2008	18803105
Determination of selected phenothiazines in human plasma by solid-phase extraction and liquid chromatography with coulometric detection.	2008 Aug 29	18706338
Capillary electrophoretic separation of tricyclic antidepressants using a polymer-coated capillary and beta-cyclodextrin as an electrolyte additive.	2008 Dec	18985667
Energetics of binding and protein unfolding upon amphiphilic drug complexation with a globular protein in different aqueous media.	2008 Jun 1	18222070
Simultaneous determination of some phenothiazine derivatives in human blood by headspace solid-phase microextraction and gas chromatography with nitrogen-phosphorus detection.	2008 Nov-Dec	19202796
Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients.	2008 Oct	19028375
[Determination of antidepressants in biological materials originating from victims of suicide by hanging].	2008 Oct-Dec	19441688
P-glycoprotein senses its substrates and the lateral membrane packing density: consequences for the catalytic cycle.	2008 Sep 23	18759452
Valproate-induced delirium in a demented patient.	2009	19836623
[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
Acute intoxication by triazolam and promazine: a case report.	2009 Jan	19306624
Simultaneous chemiluminescence determination of promazine and fluphenazine using support vector regression.	2009 Jul 15	19559917
Chemiluminescence determination of promazine in human serum and drug formulations using Ru(phen)3(2+)-Ce(IV) system and a chemometrical optimization approach.	2009 May-Jun	19253268

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