Identification

Name
Promethazine
Accession Number
DB01069  (APRD00601)
Type
Small Molecule
Groups
Approved, Investigational
Description

A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [PubChem]

Structure
Thumb
Synonyms
  • (2-dimethylamino-2-methyl)ethyl-N-dibenzoparathiazine
  • 10-(2-Dimethylaminopropyl)phenothiazine
  • 10-[2-(dimethylamino)Propyl]phenothiazine
  • N-(2'-dimethylamino-2'-Methyl)ethylphenothiazine
  • N,N,alpha-Trimethyl-10H-phenothiazine-10-ethanamine
  • N,N,α-trimethyl-10H-phenothiazine-10-ethanamine
  • Proazamine
  • Prometazina
  • Promethazine
  • Promethazinum
External IDs
Lilly 1516
Product Ingredients
IngredientUNIICASInChI Key
Promethazine hydrochlorideR61ZEH7I1I58-33-3XXPDBLUZJRXNNZ-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PhenerganSuppository25 mg/1RectalWyeth Ltd.1951-05-012008-06-30Us
PhenerganTablet50 mg/1OralWyeth Ltd.1951-05-012008-06-30Us
PhenerganTablet25 mg/1OralWyeth Ltd.1951-05-012008-06-30Us
PhenerganSuppository50 mg/1RectalWyeth Ltd.1951-05-012008-06-30Us
PhenerganSuppository12.5 mg/1RectalWyeth Ltd.1951-05-012008-06-30Us
PhenerganTablet12.5 mg/1OralWyeth Ltd.1951-05-012008-06-03Us
Phenergan Injectable 25mg/mlSolution25 mgIntramuscular; IntravenousAventis Pharma Ltd.1949-12-312005-08-01Canada
Promethazine HClInjection25 mg/1mLIntramuscular; IntravenousWatson Pharmaceuticals2006-04-05Not applicableUs
Promethazine HClInjection50 mg/1mLIntramuscular; IntravenousWatson Pharmaceuticals2006-04-05Not applicableUs
Promethazine HClSyrup6.25 mg/5mLOralANI Pharmaceuticals, Inc.2008-05-022008-05-02Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PhenadozSuppository12.5 mg/1RectalPd Rx Pharmaceuticals, Inc.2003-06-242018-02-08Us
PhenadozSuppository12.5 mg/1RectalPaddock Laboratories, Inc.2003-06-242016-11-30Us
PhenadozSuppository25 mg/1RectalRemedy Repack2016-10-202016-10-20Us
PhenadozSuppository25 mg/1RectalActavis Pharma Company2013-04-032016-05-31Us
PhenadozSuppository25 mg/1RectalActavis Pharma Company2015-02-17Not applicableUs
PhenadozSuppository12.5 mg/1RectalActavis Pharma Company2013-02-122016-11-30Us
PhenadozSuppository25 mg/1RectalPaddock Laboratories, Inc.2003-06-242016-11-30Us
PhenadozSuppository12.5 mg/1RectalActavis Pharma Company2015-03-16Not applicableUs
PhenerganInjection50 mg/1mLIntramuscularWest Ward Pharmaceutical1973-09-19Not applicableUs
PhenerganInjection50 mg/1mLIntramuscularWest Ward Pharmaceutical1973-09-19Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Histantil Tab 25mgTablet25 mgOralPharmascience Inc1983-12-31Not applicableCanada
Histantil Tab 50mgTablet50 mgOralPharmascience Inc1983-12-31Not applicableCanada
Phenergan 50Tablet50 mgOralColumbia Laboratories1996-12-312002-07-17Canada
Phenergan Cream 2%Cream2 %TopicalColumbia Laboratories1996-07-302007-07-24Canada
Phenergan Cream 2%Cream2 %TopicalRhone Poulenc Rorer1993-12-311997-08-13Canada
Phenergan Syrup 10mg/5mlSyrup10 mgOralRhone Poulenc Rorer1993-12-311996-09-09Canada
Phenergan Tablet 10mgTablet10 mgOralRhone Poulenc Rorer1993-12-311997-08-13Canada
Phenergan Tablet 25mgTablet25 mgOralNovartis1996-12-311999-07-21Canada
Phenergan Tablet 25mgTablet25 mgOralRhone Poulenc Rorer1993-12-311997-08-13Canada
Phenergan Tablet 50mgTablet50 mgOralRhone Poulenc Rorer1992-12-311997-08-13Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Dextromethorphan Hydrobromide and Promethazine HydrochloridePromethazine hydrochloride (6.25 mg/5mL) + Dextromethorphan hydrobromide monohydrate (15 mg/5mL)SyrupOralProficient Rx LP1985-01-04Not applicableUs
Dextromethorphan Hydrobromide and Promethazine HydrochloridePromethazine hydrochloride (6.25 mg/5mL) + Dextromethorphan hydrobromide monohydrate (15 mg/5mL)SyrupOralRemedy Repack2013-12-022014-12-02Us
Dextromethorphan Hydrobromide and Promethazine HydrochloridePromethazine hydrochloride (6.25 mg/5mL) + Dextromethorphan hydrobromide monohydrate (15 mg/5mL)SyrupOralAtlantic Biologicals Corps.1985-01-04Not applicableUs
Promatussin DM Adult Formula SyrPromethazine hydrochloride (6.25 mg) + Dextromethorphan hydrobromide (15 mg) + Pseudoephedrine hydrochloride (60 mg)SyrupOralWyeth Ayerst Canada Inc.1993-12-311996-09-10Canada
Promatussin DM Children FormulaPromethazine hydrochloride (3.125 mg) + Dextromethorphan hydrobromide (7.5 mg) + Pseudoephedrine hydrochloride (30 mg)LiquidOralWyeth Ltd.1981-12-311996-09-10Canada
Prometh with CodeinePromethazine hydrochloride (6.25 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL)SyrupOralRemedy Repack2013-07-082013-07-09Us
Prometh with CodeinePromethazine hydrochloride (6.25 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL)SyrupOralRebel Distributors1984-10-31Not applicableUs
Prometh with CodeinePromethazine hydrochloride (6.25 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL)SyrupOralbryant ranch prepack2003-01-032018-05-29Us
Prometh with CodeinePromethazine hydrochloride (6.25 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL)SyrupOralActavis Pharma Company1990-09-302015-06-30Us
Prometh with DextromethorphanPromethazine hydrochloride (6.25 mg/5mL) + Dextromethorphan hydrobromide monohydrate (15 mg/5mL)SyrupOralActavis Pharma Company2007-01-032011-05-31Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Meperidine Hcl and Promethazine HclPromethazine hydrochloride (25 mg/1) + Meperidine hydrochloride (50 mg/1)CapsuleOralPhysicians Total Care, Inc.2004-09-032013-01-15Us
Meperidine Hydrochloride and Promethazine HydrochloridePromethazine hydrochloride (25 mg/1) + Meperidine hydrochloride (50 mg/1)CapsuleOralEci Pharmaceuticals Llc2013-02-192018-07-24Us
Promethazine HClPromethazine hydrochloride (1 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2014-05-272017-12-06Us
Promethazine HClPromethazine hydrochloride (0.5 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2014-05-29Not applicableUs
Promethazine HClPromethazine hydrochloride (0.625 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2014-05-27Not applicableUs
International/Other Brands
Avomine / Fargan / Farganesse / Lergigan / Prothiazine / Receptozine / Romergan
Categories
UNII
FF28EJQ494
CAS number
60-87-7
Weight
Average: 284.419
Monoisotopic: 284.13471934
Chemical Formula
C17H20N2S
InChI Key
PWWVAXIEGOYWEE-UHFFFAOYSA-N
InChI
InChI=1S/C17H20N2S/c1-13(18(2)3)12-19-14-8-4-6-10-16(14)20-17-11-7-5-9-15(17)19/h4-11,13H,12H2,1-3H3
IUPAC Name
dimethyl[1-(10H-phenothiazin-10-yl)propan-2-yl]amine
SMILES
CC(CN1C2=CC=CC=C2SC2=CC=CC=C12)N(C)C

Pharmacology

Indication

For the treatment of allergic disorders, and nausea/vomiting.

Associated Conditions
Associated Therapies
Pharmacodynamics

Promethazine, a phenothiazine, is an H1-antagonist with anticholinergic, sedative, and antiemetic effects and some local anesthetic properties. Promethazine is used as an antiemetic or to prevent motion sickness.

Mechanism of action

Like other H1-antagonists, promethazine competes with free histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. The relief of nausea appears to be related to central anticholinergic actions and may implicate activity on the medullary chemoreceptor trigger zone.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
UD(2) dopamine receptor
antagonist
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
UMuscarinic acetylcholine receptor M4
antagonist
Human
UMuscarinic acetylcholine receptor M5
antagonist
Human
UAlpha-1A adrenergic receptor
unknown
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
UCalmodulin
inhibitor
Human
UHistamine H2 receptor
antagonist
Human
Absorption

On average, 88% of a promethazine dose is absorbed after oral administration; however, the absolute bioavailability is only 25% because of first-pass clearance.

Volume of distribution
Not Available
Protein binding

93%

Metabolism

Hepatic

Route of elimination

Promethazine hydrochloride is metabolized in the liver, with the sulfoxides of promethazine and N-desmethylpromethazine being the predominant metabolites appearing in the urine.

Half life

16-19 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex). LD50=55mg/kg (I.V. in mice)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Promethazine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Promethazine is combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Promethazine.
1,10-PhenanthrolineThe therapeutic efficacy of Promethazine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Promethazine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Promethazine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Promethazine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Promethazine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Promethazine is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Promethazine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Promethazine is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
  • Take with food to reduce irritation. Avoid alcohol.

References

Synthesis Reference
US2530451
General References
  1. Peters RJ Jr, Kelder SH, Markham CM, Yacoubian GS Jr, Peters LA, Ellis A: Beliefs and social norms about codeine and promethazine hydrochloride cough syrup (CPHCS) onset and perceived addiction among urban Houstonian adolescents: an addiction trend in the city of lean. J Drug Educ. 2003;33(4):415-25. [PubMed:15237866]
External Links
Human Metabolome Database
HMDB0015202
KEGG Drug
D00494
KEGG Compound
C07404
PubChem Compound
4927
PubChem Substance
46507798
ChemSpider
4758
BindingDB
50017696
ChEBI
8461
ChEMBL
CHEMBL643
Therapeutic Targets Database
DAP000334
PharmGKB
PA451128
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Promethazine
ATC Codes
V03AB05 — Prednisolone and promethazineR06AD02 — PromethazineD04AA10 — PromethazineR06AD52 — Promethazine, combinations
AHFS Codes
  • 28:24.92 — Miscellaneous Anxiolytics Sedatives and Hypnotics
  • 04:04.12 — Phenothiazine Derivatives
FDA label
Download (93.4 KB)
MSDS
Download (74.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentAllergies1
2RecruitingTreatmentCrohn's Disease (CD)1
2TerminatedTreatmentDiabetic Gastroparesis1
2, 3CompletedNot AvailableLabour Pain1
3CompletedPreventionNausea / Pain NOS / Vomiting1
3CompletedTreatmentMigraine With Aura / Migraine Without Aura1
3CompletedTreatmentNausea / Pain NOS / Vomiting1
3CompletedTreatmentVertigo, Peripheral1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentHyperemesis Gravidarum1
3Unknown StatusHealth Services ResearchSedation, Conscious1
4CompletedBasic ScienceVestibular1
4CompletedPreventionNausea / Postoperative Nausea and Vomiting (PONV)1
4CompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
4CompletedTreatmentChronic Hepatitis C Infection With Hepatic Coma / Hepatic Failure / Hepatic Impairment1
4CompletedTreatmentNausea / Vomiting1
4CompletedTreatmentSnake Bites1
4RecruitingTreatmentAcute Agitation / Aggressive Behavior / Psychiatric Emergency1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
Not AvailableCompletedTreatmentPsychomotor Agitation1
Not AvailableRecruitingBasic ScienceStaphylococcus Aureus1
Not AvailableRecruitingSupportive CareCancer, Breast / Post-Operative Nausea and Vomiting (PONV)1
Not AvailableTerminatedPreventionAmbulatory Gynecological Laparoscopic Procedures1
Not AvailableTerminatedPreventionNausea1
Not AvailableTerminatedTreatmentNausea1
Not AvailableUnknown StatusSupportive CareEndoscopic Retrograde Cholangiopancreatography (ERCP) / Endoscopic Ultrasound (EUS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Aidarex Pharmacuticals LLC
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Baxter International Inc.
  • Bioniche Pharma
  • Blenheim Pharmacal
  • Bryant Ranch Prepack
  • C.O. Truxton Inc.
  • Cadila Healthcare Ltd.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Century Pharmaceuticals Inc.
  • Clint Pharmaceutical Inc.
  • Comprehensive Consultant Services Inc.
  • Consolidated Midland Corp.
  • Corepharma LLC
  • Dee Stevens and Son Feeder
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Ebewe Pharma
  • G & W Labs
  • General Injectables and Vaccines Inc.
  • Global Pharmaceuticals
  • Goldline Laboratories Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hi Tech Pharmacal Co. Inc.
  • Hikma Pharmaceuticals
  • Hospira Inc.
  • Impax Laboratories Inc.
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • KVK-Tech Inc.
  • Lake Erie Medical and Surgical Supply
  • Lark Pharmaceuticals Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Martica Enterprises Inc.
  • Martin Surgical Supply
  • Mckesson Corp.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Nubenco Enterprises Inc.
  • Nucare Pharmaceuticals Inc.
  • Paddock Labs
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharmaceutical Association
  • Pharmacy Service Center
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Sun Pharmaceutical Industries Ltd.
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral
Injection, solutionIntramuscular50 mg/1mL
SuppositoryRectal50 mg/1
CreamTopical2 %
SolutionIntramuscular; Intravenous25 mg
SyrupOral10 mg
TabletOral10 mg
TabletOral25 mg
TabletOral50 mg
SyrupOral
LiquidOral
InjectionIntramuscular50 mg/1mL
InjectionIntramuscular; Intravenous25 mg/1mL
InjectionIntramuscular; Intravenous50 mg/1mL
Injection, solutionIntravenous0.5 mg/1mL
Injection, solutionIntravenous0.625 mg/1mL
Injection, solutionIntravenous1 mg/1mL
LiquidIntramuscular; Intravenous28.2 mg
InjectionIntramuscular25 mg/1mL
Injection, solutionIntramuscular25 mg/1
Injection, solutionIntramuscular; Intravenous25 mg/1mL
Injection, solutionIntramuscular; Intravenous50 mg/1mL
SolutionOral6.25 mg/5mL
SuppositoryRectal12.5 mg/1
SuppositoryRectal25 mg/1
SyrupOral6.25 mg/5mL
TabletOral12.5 mg/1
TabletOral25 mg/1
TabletOral25 mg/301
TabletOral50 1/1
TabletOral50 mg/1
SolutionOral
LiquidIntramuscular; Intravenous25 mg
Prices
Unit descriptionCostUnit
Promethegan 12 50 mg Suppository Box101.64USD box
Phenergan 12 50 mg Suppository Box80.16USD box
Phenergan 12 25 mg Suppository Box62.59USD box
Promethegan 12 25 mg Suppository Box62.27USD box
Promethazine HCl 12 50 mg Suppository Box60.94USD box
Phenergan 12 12.5 mg Suppository Box54.58USD box
Phenergan 25 mg suppository8.32USD suppository
Promethegan 50 mg suppository8.14USD suppository
Phenergan 12.5 mg suppository7.94USD suppository
Phenergan 50 mg suppository7.39USD suppository
Promethazine 50 mg suppository4.88USD suppository
Promethegan 25 mg suppository4.62USD suppository
Phenadoz 25 mg suppository4.45USD suppository
Promethazine 25 mg suppository4.32USD suppository
Promethegan 12.5 mg suppository4.02USD suppository
Promethazine HCl 12.5 mg Suppository4.0USD suppository
Phenadoz 12.5 mg suppository3.89USD suppository
Phenergan 25 mg/ml ampul3.84USD ml
Promethazine 12.5 mg suppository3.82USD suppository
Phenergan 50 mg/ml ampul3.68USD ml
Promethazine HCl 50 mg/ml Solution 1ml Ampule2.8USD ampule
Promethazine 50 mg/ml ampul2.25USD ml
Promethazine hcl powder2.14USD g
Promethazine 25 mg/ml ampul1.1USD ml
Promethazine 25 mg/ml1.06USD ml
Promethazine HCl 50 mg tablet0.81USD tablet
Promethazine 50 mg tablet0.78USD tablet
Promethazine HCl 25 mg tablet0.73USD tablet
Phenergan 25 mg tablet0.62USD tablet
Promethazine 25 mg tablet0.51USD tablet
Promethazine 12.5 mg tablet0.49USD tablet
Promethazine-DM 6.25-15 mg/5ml Syrup0.18USD ml
Promethazine HCl 6.25 mg/5ml Syrup0.11USD ml
Promethazine VC Plain 6.25-5 mg/5ml Syrup0.09USD ml
Promethazine-Codeine 6.25-10 mg/5ml Syrup0.06USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)60 °CPhysProp
boiling point (°C)190-192 °C at 3.00E+00 mm HgPhysProp
water solubility15.6 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.81HANSCH,C ET AL. (1995)
logS-4.26ADME Research, USCD
pKa9.1SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0245 mg/mLALOGPS
logP4.52ALOGPS
logP4.29ChemAxon
logS-4.1ALOGPS
pKa (Strongest Basic)9.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity88.5 m3·mol-1ChemAxon
Polarizability32.38 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9832
Blood Brain Barrier+0.9855
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.8157
P-glycoprotein inhibitor IInhibitor0.8408
P-glycoprotein inhibitor IINon-inhibitor0.6473
Renal organic cation transporterInhibitor0.5156
CYP450 2C9 substrateNon-substrate0.7736
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5338
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9341
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.567
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9088
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6959 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9786
hERG inhibition (predictor II)Inhibitor0.7661
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.88 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - CI-BGC-MSsplash10-000i-0090000000-f1fe9756bed13819bbb4
GC-MS Spectrum - EI-BGC-MSsplash10-00di-9000000000-abbdf5514dccef4821b2
GC-MS Spectrum - EI-BGC-MSsplash10-00di-9100000000-9bef9a6b83d662fc7e2c
GC-MS Spectrum - CI-BGC-MSsplash10-0079-8290000000-fe5d6b4e9f62b7270798
Mass Spectrum (Electron Ionization)MSsplash10-00di-9210000000-7167670dff3395a6ade2
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000j-0690000000-0b4dfbac9712d2e36046
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-9220000000-9d761be1437f10dcc94b

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / Benzenoids / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Para-thiazine / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Thioether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, tertiary amine (CHEBI:8461)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Suzuki A, Yasui-Furukori N, Mihara K, Kondo T, Furukori H, Inoue Y, Kaneko S, Otani K: Histamine H1-receptor antagonists, promethazine and homochlorcyclizine, increase the steady-state plasma concentrations of haloperidol and reduced haloperidol. Ther Drug Monit. 2003 Apr;25(2):192-6. [PubMed:12657913]
  3. Smith BN, Armstrong WE: Histamine enhances the depolarizing afterpotential of immunohistochemically identified vasopressin neurons in the rat supraoptic nucleus via H1-receptor activation. Neuroscience. 1993 Apr;53(3):855-64. [PubMed:8098142]
  4. Miller RA, Tu AT: Factors in snake venoms that increase capillary permeability. J Pharm Pharmacol. 1989 Nov;41(11):792-4. [PubMed:2576052]
  5. Claro E, Arbones L, Garcia A, Picatoste F: Phosphoinositide hydrolysis mediated by histamine H1-receptors in rat brain cortex. Eur J Pharmacol. 1986 Apr 16;123(2):187-96. [PubMed:3011460]
  6. Ikeda H, Kubo N, Nakamura A, Harada N, Minamino M, Yamashita T: Histamine-induced calcium released from cultured human mucosal microvascular endothelial cells from nasal inferior turbinate. Acta Otolaryngol. 1997 Nov;117(6):864-70. [PubMed:9442829]
  7. Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97. [PubMed:2866055]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Golembiewski JA, O'Brien D: A systematic approach to the management of postoperative nausea and vomiting. J Perianesth Nurs. 2002 Dec;17(6):364-76. [PubMed:12476402]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Golembiewski JA, O'Brien D: A systematic approach to the management of postoperative nausea and vomiting. J Perianesth Nurs. 2002 Dec;17(6):364-76. [PubMed:12476402]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Golembiewski JA, O'Brien D: A systematic approach to the management of postoperative nausea and vomiting. J Perianesth Nurs. 2002 Dec;17(6):364-76. [PubMed:12476402]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Golembiewski JA, O'Brien D: A systematic approach to the management of postoperative nausea and vomiting. J Perianesth Nurs. 2002 Dec;17(6):364-76. [PubMed:12476402]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Golembiewski JA, O'Brien D: A systematic approach to the management of postoperative nausea and vomiting. J Perianesth Nurs. 2002 Dec;17(6):364-76. [PubMed:12476402]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. Golembiewski JA, O'Brien D: A systematic approach to the management of postoperative nausea and vomiting. J Perianesth Nurs. 2002 Dec;17(6):364-76. [PubMed:12476402]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Unknown
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Bileviciute I, Stenfors C, Theodorsson E, Lundeberg T: Unilateral injection of calcitonin gene-related peptide (CGRP) induces bilateral oedema formation and release of CGRP-like immunoreactivity in the rat hindpaw. Br J Pharmacol. 1998 Nov;125(6):1304-12. [PubMed:9863661]
  2. Kelley BM, Porter JH: The role of muscarinic cholinergic receptors in the discriminative stimulus properties of clozapine in rats. Pharmacol Biochem Behav. 1997 Aug;57(4):707-19. [PubMed:9258998]
  3. Hoenicke EM, Vanecek SA, Woods JH: The discriminative stimulus effects of clozapine in pigeons: involvement of 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors. J Pharmacol Exp Ther. 1992 Oct;263(1):276-84. [PubMed:1403790]
  4. Martinez F, Coleman JW: A comparison of the effects of chlorpromazine and more selective histamine and 5-hydroxytryptamine antagonists on human IgG synthesis in vitro. Int J Immunopharmacol. 1990;12(2):185-91. [PubMed:2329012]
  5. Fiorella D, Rabin RA, Winter JC: The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis. Psychopharmacology (Berl). 1995 Oct;121(3):347-56. [PubMed:8584617]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Titin binding
Specific Function
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name
CALM1
Uniprot ID
P0DP23
Uniprot Name
Calmodulin
Molecular Weight
16837.47 Da
References
  1. Cohen ME, Sharp GW, Donowitz M: Suggestion of a role for calmodulin and phosphorylation in regulation of rabbit ileal electrolyte transport: effects of promethazine. Am J Physiol. 1986 Nov;251(5 Pt 1):G710-7. [PubMed:3022601]
  2. Scott JA, Khaw BA, Fallon JT, Locke E, Rabito CA, Peto CA, Homcy CJ: The effect of phenothiazines upon maintenance of membrane integrity in the cultured myocardial cell. J Mol Cell Cardiol. 1986 Dec;18(12):1243-54. [PubMed:3820316]
  3. Lohr KM, Feix JB, Kurth C: Chlorpromazine inhibits neutrophil chemotaxis beyond the chemotactic receptor-ligand interaction. J Infect Dis. 1984 Nov;150(5):643-52. [PubMed:6092486]
  4. DiPaola M, Keith CH, Feldman D, Tycko B, Maxfield FR: Loss of alpha 2-macroglobulin and epidermal growth factor surface binding induced by phenothiazines and naphthalene sulfonamides. J Cell Physiol. 1984 Feb;118(2):193-202. [PubMed:6319437]
  5. Luchowski EM, Yousif F, Triggle DJ, Maurer SC, Sarmiento JG, Janis RA: Effects of metal cations and calmodulin antagonists on [3H] nitrendipine binding in smooth and cardiac muscle. J Pharmacol Exp Ther. 1984 Sep;230(3):607-13. [PubMed:6433001]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Dick W, Lorenz W, Heintz D, Sitter H, Doenicke A: [Histamine release during induction of combination anesthesia using nalbuphine or fentanyl. Modulation of the reaction by premedication with promethazine/pethidine]. Anaesthesist. 1992;41(5):239-47. [PubMed:1377455]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Platts SH, Shi SJ, Meck JV: Akathisia with combined use of midodrine and promethazine. JAMA. 2006 May 3;295(17):2000-1. [PubMed:16670408]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Potential CYP2B6 Substrates, Inhibitors, Inudcers (https://ctep.cancer.gov/protocoldevelopment/docs/cyp2b6.doc) [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ibrahim S, Peggins J, Knapton A, Licht T, Aszalos A: Influence of antipsychotic, antiemetic, and Ca(2+) channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation. J Pharmacol Exp Ther. 2000 Dec;295(3):1276-83. [PubMed:11082465]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:49