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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2018-05-20 20:15:51 UTC
HMDB IDHMDB0015202
Secondary Accession Numbers
  • HMDB15202
Metabolite Identification
Common NamePromethazine
DescriptionPromethazine is only found in individuals that have used or taken this drug. It is 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]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.
Structure
Thumb
Synonyms
ValueSource
(2-dimethylamino-2-Methyl)ethyl-N-dibenzoparathiazineChEBI
10-(2-Dimethylaminopropyl)phenothiazineChEBI
10-[2-(dimethylamino)Propyl]phenothiazineChEBI
N,N,alpha-Trimethyl-10H-phenothiazine-10-ethanamineChEBI
N-(2'-dimethylamino-2'-Methyl)ethylphenothiazineChEBI
ProazamineChEBI
PrometazinaChEBI
PromethazinumChEBI
N,N,a-Trimethyl-10H-phenothiazine-10-ethanamineGenerator
N,N,α-trimethyl-10H-phenothiazine-10-ethanamineGenerator
IsopromethazineHMDB
Lilly 1516HMDB
ProazaimineHMDB
PromazinamideHMDB
PrometazineHMDB
PromethazinHMDB
PromethiazineHMDB
PromezathineHMDB
ProthazinHMDB
ProthazineHMDB
DiprazinMeSH
RumerganMeSH
PhenarganMeSH
PhensedylMeSH
PrometMeSH
Promethazine hydrochlorideMeSH
RemsedMeSH
PrometazinMeSH
PyrethiaMeSH
AtosilMeSH
DipherganMeSH
Hydrochloride, promethazineMeSH
PhenerganMeSH
PipolfenMeSH
PipolphenMeSH
Chemical FormulaC17H20N2S
Average Molecular Weight284.419
Monoisotopic Molecular Weight284.13471934
IUPAC Namedimethyl[1-(10H-phenothiazin-10-yl)propan-2-yl]amine
Traditional Namepromethazine
CAS Registry Number60-87-7
SMILES
CC(CN1C2=CC=CC=C2SC2=CC=CC=C12)N(C)C
InChI Identifier
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
InChI KeyPWWVAXIEGOYWEE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Aryl thioether
  • Tertiary aliphatic/aromatic amine
  • Para-thiazine
  • Benzenoid
  • Tertiary amine
  • Tertiary aliphatic amine
  • Thioether
  • Azacycle
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point60 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.024 g/LNot Available
LogP4.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.024 g/LALOGPS
logP4.52ALOGPS
logP4.29ChemAxon
logS-4.1ALOGPS
pKa (Strongest Basic)9.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity88.5 m³·mol⁻¹ChemAxon
Polarizability32.38 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-000i-0090000000-f1fe9756bed13819bbb4View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-9000000000-abbdf5514dccef4821b2View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-9100000000-9bef9a6b83d662fc7e2cView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0079-8290000000-fe5d6b4e9f62b7270798View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-000i-0090000000-f1fe9756bed13819bbb4View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-9000000000-abbdf5514dccef4821b2View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-9100000000-9bef9a6b83d662fc7e2cView in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0079-8290000000-fe5d6b4e9f62b7270798View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0229-9150000000-19753aa755aa19143e9bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000j-0690000000-0b4dfbac9712d2e36046View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-9220000000-9d761be1437f10dcc94bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-2090000000-76a910470a52a47a6757View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000f-8090000000-d597b4b7604e8276f449View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00dr-9110000000-cbed4a551fc77cf0e5b9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-e24a248a31f0e31f1ec5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-009t-0940000000-afb556a81c40edffb9a1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-3910000000-3daef27d94a5cac7d4a7View in MoNA
MSMass Spectrum (Electron Ionization)splash10-00di-9210000000-7167670dff3395a6ade2View in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01069 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01069 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01069
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4758
KEGG Compound IDC07404
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkPromethazine
METLIN IDNot Available
PubChem Compound4927
PDB IDNot Available
ChEBI ID8461
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
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 ]

Only showing the first 10 proteins. There are 14 proteins in total.

Enzymes

General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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 ]
General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
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 ]
General function:
Involved in calcium ion binding
Specific function:
Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis
Gene Name:
CALM1
Uniprot ID:
P62158
Molecular weight:
16837.5
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular weight:
55783.6
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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) proteins
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular weight:
51486.0
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 action of G proteins. Primary transducing effect is Pi turnover
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular weight:
66127.4
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 action of G proteins. Primary transducing effect is Pi turnover
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular weight:
51420.4
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 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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 ]

Only showing the first 10 proteins. There are 14 proteins in total.