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Identification
NamePhenacetin
Accession NumberDB03783  (DB08243, EXPT03306)
Typesmall molecule
Groupswithdrawn
Description

Phenacetin was withdrawn from the Canadian market in June 1973 due to concerns regarding nephropathy (damage to or disease of the kidney).

Structure
Thumb
Synonyms
SynonymLanguageCode
AcetophenetidinNot AvailableNot Available
AcetophenetidineNot AvailableNot Available
AcetophenetinNot AvailableNot Available
AcetphenetidinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AchrocidinNot Available
CodempiralNot Available
CommotionalNot Available
ContradolNot Available
ContradouleurNot Available
Brand mixturesNot Available
Categories
CAS number62-44-2
WeightAverage: 179.2157
Monoisotopic: 179.094628665
Chemical FormulaC10H13NO2
InChI KeyCPJSUEIXXCENMM-UHFFFAOYSA-N
InChI
InChI=1S/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H,3H2,1-2H3,(H,11,12)
IUPAC Name
N-(4-ethoxyphenyl)acetamide
SMILES
CCOC1=CC=C(NC(C)=O)C=C1
Mass Specshow(8.59 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassAnilides
Direct parentAnilides
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Secondary Carboxylic Acid Amides; Enolates; Carboxylic Acids; Polyamines
Substituentsphenol ether; alkyl aryl ether; secondary carboxylic acid amide; carboxamide group; carboxylic acid derivative; enolate; carboxylic acid; ether; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Pharmacology
IndicationUsed principally as an analgesic.
PharmacodynamicsPhenacetin was the first NSAID and fever reducer to go on the market. Its analgesic effects are due to its actions on the sensory tracts of the spinal cord. In addition, phenacetin has a depressant action of the heart, where it acts as a negative inotrope. It is an antipyretic, acting on the brain to decrease the temperature set point. It is also used to treat rheumatoid arthritis (subacute type), intercostal neuralgia, and some forms of ataxia. [Wikipedia]
Mechanism of actionPhenacetin's analgesic effects are due to its actions on the sensory tracts of the spinal cord. In addition, phenacetin has a depressant action on the heart, where it acts as a negative inotrope. It is an antipyretic, acting on the brain to decrease the temperature set point. It is also used to treat rheumatoid arthritis (subacute type) and intercostal neuralgia. [Wikipedia]
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Metabolised in the body to paracetamol.

SubstrateEnzymesProduct
Phenacetin
acetaminophenDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityAcute oral toxicity (LD50): 866 mg/kg [Mouse].
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9915
Caco-2 permeable + 0.8867
P-glycoprotein substrate Non-substrate 0.8257
P-glycoprotein inhibitor I Non-inhibitor 0.9091
P-glycoprotein inhibitor II Non-inhibitor 0.9391
Renal organic cation transporter Non-inhibitor 0.889
CYP450 2C9 substrate Non-substrate 0.8154
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.5542
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9619
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5441
Ames test AMES toxic 0.9108
Carcinogenicity Non-carcinogens 0.6859
Biodegradation Ready biodegradable 0.5762
Rat acute toxicity 2.0676 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9679
hERG inhibition (predictor II) Non-inhibitor 0.9315
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point137.5 °CPhysProp
water solubility766 mg/L (at 25 °C)SEIDELL,A (1941)
logP1.58NAKAGAWA,Y ET AL. (1992)
logS-2.37ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility1.78e+00 g/lALOGPS
logP1.62ALOGPS
logP1.41ChemAxon
logS-2ALOGPS
pKa (strongest acidic)14.98ChemAxon
pKa (strongest basic)-4.2ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area38.33ChemAxon
rotatable bond count3ChemAxon
refractivity52.13ChemAxon
polarizability19.82ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Ernst Bocker, Wolfgang Kracht, Roland Rupp, Erhard Schellmann, Viktor Trescher, Martin Ullrich, “Preparation of melt-sprayed spherical phenacetin granules.” U.S. Patent US4086346, issued October, 1972.

US4086346
General Reference
  1. Dubach UC, Rosner B, Sturmer T: An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987) N Engl J Med. 1991 Jan 17;324(3):155-60. Pubmed
  2. Cochran AJ, Lawson DH, Linton AL: Renal papillary necrosis following phenacetin excess. Scott Med J. 1967 Jul;12(7):246-50. Pubmed
  3. TAN GH, RABBINO MD, HOPPER J Jr: IS PHENACETIN A NEPHROTOXIN?A REPORT ON TWENTY-THREE USERS OF THE DRUG. Calif Med. 1964 Aug;101:73-7. Pubmed
  4. Brix AE: Renal papillary necrosis. Toxicol Pathol. 2002 Nov-Dec;30(6):672-4. Pubmed
External Links
ResourceLink
KEGG DrugD00569
KEGG CompoundC07591
PubChem Compound4754
PubChem Substance46507394
ChemSpider4590
ChEBI8050
ChEMBL
Therapeutic Targets DatabaseDNC001117
PharmGKBPA450897
WikipediaPhenacetin
ATC CodesN02BE03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(50.3 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Epub 2009 Nov 24. Pubmed
  3. Zhang T, Zhu Y, Gunaratna C: Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):371-9. Pubmed
  4. Kobayashi K, Nakajima M, Oshima K, Shimada N, Yokoi T, Chiba K: Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes. Drug Metab Dispos. 1999 Aug;27(8):860-5. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2A13

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2A13 Q16696 Details

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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

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. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. Pubmed
  2. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:22