Phenacetin

Identification

Generic Name
Phenacetin
DrugBank Accession Number
DB03783
Background

Phenacetin was withdrawn from the Canadian market in June 1973 due to concerns regarding nephropathy (damage to or disease of the kidney).

Type
Small Molecule
Groups
Withdrawn
Structure
Weight
Average: 179.2157
Monoisotopic: 179.094628665
Chemical Formula
C10H13NO2
Synonyms
  • Acetophenetidin
  • Acetophenetidine
  • Acetophenetin
  • Acetphenetidin
  • Fenacetina
  • Phenacetin
External IDs
  • NSC-7651

Pharmacology

Indication

Used principally as an analgesic.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Phenacetin was the first NSAID and fever reducer to go on the market. It acts as an analgesic at the spinal cord as well as a negative inotrope at the heart. It can be used to treat subacute rheumatoid arthritis, intercostal neuralgia, and ataxias.

Mechanism of action
TargetActionsOrganism
UProstaglandin G/H synthase 1Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Metabolised in the body to paracetamol.

Hover over products below to view reaction partners

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Acute oral toxicity (LD50): 866 mg/kg [Mouse].

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Phenacetin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Phenacetin can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Phenacetin can be increased when it is combined with Abiraterone.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Phenacetin.
AcebutololThe metabolism of Phenacetin can be decreased when combined with Acebutolol.
Food Interactions
Not Available

Products

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International/Other Brands
Achrocidin / Codempiral / Commotional / Contradol / Contradouleur

Categories

ATC Codes
N02BE73 — Phenacetin, combinations with psycholepticsN02BE03 — PhenacetinN02BE53 — Phenacetin, combinations excl. psycholeptics
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as acetanilides. These are organic compounds containing an acetamide group conjugated to a phenyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Acetanilides
Alternative Parents
N-acetylarylamines / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Acetamides / Secondary carboxylic acid amides / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Acetamide / Acetanilide / Alkyl aryl ether / Aromatic homomonocyclic compound / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Ether / Hydrocarbon derivative / N-acetylarylamine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, acetamides (CHEBI:8050)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
ER0CTH01H9
CAS number
62-44-2
InChI Key
CPJSUEIXXCENMM-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

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 References
  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. [Article]
  2. Cochran AJ, Lawson DH, Linton AL: Renal papillary necrosis following phenacetin excess. Scott Med J. 1967 Jul;12(7):246-50. [Article]
  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. [Article]
  4. Brix AE: Renal papillary necrosis. Toxicol Pathol. 2002 Nov-Dec;30(6):672-4. [Article]
KEGG Drug
D00569
KEGG Compound
C07591
PubChem Compound
4754
PubChem Substance
46507394
ChemSpider
4590
BindingDB
50420191
RxNav
8113
ChEBI
8050
ChEMBL
CHEMBL16073
ZINC
ZINC000000000602
Therapeutic Targets Database
DNC001117
PharmGKB
PA450897
PDBe Ligand
N4E
Wikipedia
Phenacetin
PDB Entries
3ebs
MSDS
Download (50.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableRenal Failure, Chronic Renal Failure1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)137.5 °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 Solubility1.78 mg/mLALOGPS
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 Area38.33 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity52.13 m3·mol-1Chemaxon
Polarizability19.82 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9915
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.8257
P-glycoprotein inhibitor INon-inhibitor0.9091
P-glycoprotein inhibitor IINon-inhibitor0.9391
Renal organic cation transporterNon-inhibitor0.889
CYP450 2C9 substrateNon-substrate0.8154
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.5542
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9619
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5441
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.6859
BiodegradationReady biodegradable0.5762
Rat acute toxicity2.0676 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9679
hERG inhibition (predictor II)Non-inhibitor0.9315
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.59 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - CI-BGC-MSsplash10-001i-0900000000-335c6f93c6c61172faca
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-3900000000-a251ba59f8f792deb3e1
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-03di-6900100000-e5425770c8b511b991fa
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-ff1bc2f7f827dd1711f6
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01qi-0900000000-8d7f58b56528e6f12b90
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0900000000-632d2f940d3bf1e4b090
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-2900000000-a8b75ec081cf2f9bd170
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0c03-2900000000-115f1b03c65a7dc2e1e9
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0900000000-375522dc595b7e227b62
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-6900100000-e5425770c8b511b991fa
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0019-0900000000-70fe2ead25d848a41bb4
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0900000000-c616bec1a8c0e33289d7
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-1900000000-4bbe6c96ff088515bc5e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-05mo-9600000000-8d806afb73c7b40951ea
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-067i-7900000000-e320de2cebb57564d173
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00lr-1900000000-58597e18cf0002e9034c
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-148.6679959
predicted
DarkChem Lite v0.1.0
[M-H]-148.6039959
predicted
DarkChem Lite v0.1.0
[M-H]-149.4410959
predicted
DarkChem Lite v0.1.0
[M-H]-137.53775
predicted
DeepCCS 1.0 (2019)
[M+H]+150.0604959
predicted
DarkChem Lite v0.1.0
[M+H]+149.8287959
predicted
DarkChem Lite v0.1.0
[M+H]+150.1993959
predicted
DarkChem Lite v0.1.0
[M+H]+141.36508
predicted
DeepCCS 1.0 (2019)
[M+Na]+160.6199486
predicted
DarkChem Lite v0.1.0
[M+Na]+149.0467959
predicted
DarkChem Lite v0.1.0
[M+Na]+149.3789959
predicted
DarkChem Lite v0.1.0
[M+Na]+150.59239
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-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
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO: Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7. [Article]
  2. Echizen H, Tanizaki M, Tatsuno J, Chiba K, Berwick T, Tani M, Gonzalez FJ, Ishizaki T: Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans. Drug Metab Dispos. 2000 Aug;28(8):937-44. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-s...
Gene Name
CYP2A13
Uniprot ID
Q16696
Uniprot Name
Cytochrome P450 2A13
Molecular Weight
56687.095 Da
References
  1. Fukami T, Nakajima M, Sakai H, Katoh M, Yokoi T: CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline. Drug Metab Dispos. 2007 Mar;35(3):335-9. doi: 10.1124/dmd.106.011064. Epub 2006 Dec 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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. [Article]
Kind
Protein
Organism
Humans
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  2. Nakajima M, Kobayashi K, Oshima K, Shimada N, Tokudome S, Chiba K, Yokoi T: Activation of phenacetin O-deethylase activity by alpha-naphthoflavone in human liver microsomes. Xenobiotica. 1999 Sep;29(9):885-98. doi: 10.1080/004982599238137 . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. 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. [Article]
  2. 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. [Article]
  3. Huang Q, Deshmukh RS, Ericksen SS, Tu Y, Szklarz GD: Preferred binding orientations of phenacetin in CYP1A1 and CYP1A2 are associated with isoform-selective metabolism. Drug Metab Dispos. 2012 Dec;40(12):2324-31. doi: 10.1124/dmd.112.047308. Epub 2012 Sep 4. [Article]
  4. Yun CH, Miller GP, Guengerich FP: Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis. Biochemistry. 2001 Apr 10;40(14):4521-30. [Article]
  5. Grimm SW, Dyroff MC: Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997 May;25(5):598-602. [Article]
  6. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Flockhart Table of Drug Interactions [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
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. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 21, 2021 18:51