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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Phenacetin
- Accession Number
- DB03783 (EXPT03306, DB08243)
- Type
- Small Molecule
- Groups
- Withdrawn
- Description
Phenacetin was withdrawn from the Canadian market in June 1973 due to concerns regarding nephropathy (damage to or disease of the kidney).
- Structure
Structure for Phenacetin (DB03783)
- Synonyms
- Acetophenetidin
- Acetophenetidine
- Acetophenetin
- Acetphenetidin
- Fenacetina
- Phenacetin
- External IDs
- NSC-7651
- International/Other Brands
- Achrocidin / Codempiral / Commotional / Contradol / Contradouleur
- Categories
- Acetanilides
- Amides
- Amines
- Analgesics
- Analgesics, Non-Narcotic
- Anilides
- Aniline Compounds
- Central Nervous System Agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2A6 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Nervous System
- OAT1/SLC22A6 inhibitors
- Peripheral Nervous System Agents
- Sensory System Agents
- UNII
- ER0CTH01H9
- CAS number
- 62-44-2
- Weight
- Average: 179.2157
Monoisotopic: 179.094628665 - Chemical Formula
- C10H13NO2
- 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
Pharmacology
- Indication
Used principally as an analgesic.
- 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
Target Actions Organism UProstaglandin G/H synthase 1 Not Available Humans - Absorption
- Not Available
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
Metabolised in the body to paracetamol.
- Route of elimination
- Not Available
- Half life
- Not Available
- Clearance
- Not Available
- Toxicity
Acute oral toxicity (LD50): 866 mg/kg [Mouse].
- Affected organisms
- Humans and other mammals
- 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.
Drug Interaction Unlock Additional Data(R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Phenacetin. (S)-Warfarin The metabolism of (S)-Warfarin can be decreased when combined with Phenacetin. 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine The metabolism of Phenacetin can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine. 4-Methoxyamphetamine The metabolism of Phenacetin can be decreased when combined with 4-Methoxyamphetamine. 5-methoxy-N,N-dimethyltryptamine The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Phenacetin. 6-O-benzylguanine The metabolism of 6-O-benzylguanine can be decreased when combined with Phenacetin. 8-azaguanine The metabolism of Phenacetin can be decreased when combined with 8-azaguanine. 8-chlorotheophylline The metabolism of 8-chlorotheophylline can be decreased when combined with Phenacetin. 9-Deazaguanine The metabolism of 9-Deazaguanine can be decreased when combined with Phenacetin. 9-Methylguanine The metabolism of Phenacetin can be decreased when combined with 9-Methylguanine. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not 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 References
- 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:1984193]
- Cochran AJ, Lawson DH, Linton AL: Renal papillary necrosis following phenacetin excess. Scott Med J. 1967 Jul;12(7):246-50. [PubMed:6036245]
- 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:14180501]
- Brix AE: Renal papillary necrosis. Toxicol Pathol. 2002 Nov-Dec;30(6):672-4. [PubMed:12512867]
- External Links
- 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
- ATC Codes
- N02BE73 — Phenacetin, combinations with psycholepticsN02BE03 — PhenacetinN02BE53 — Phenacetin, combinations excl. psycholeptics
- PDB Entries
- 3ebs
- MSDS
- Download (50.3 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count Not Available Completed Not Available Chronic Renal Failure (CRF) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 137.5 °C PhysProp water solubility 766 mg/L (at 25 °C) SEIDELL,A (1941) logP 1.58 NAKAGAWA,Y ET AL. (1992) logS -2.37 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 1.78 mg/mL ALOGPS logP 1.62 ALOGPS logP 1.41 ChemAxon logS -2 ALOGPS pKa (Strongest Acidic) 14.98 ChemAxon pKa (Strongest Basic) -4.2 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 38.33 Å2 ChemAxon Rotatable Bond Count 3 ChemAxon Refractivity 52.13 m3·mol-1 ChemAxon Polarizability 19.82 Å3 ChemAxon Number of Rings 1 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - 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 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Download (8.59 KB)
- Spectra
Taxonomy
- 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
- Acetanilide / N-acetylarylamine / Phenoxy compound / Phenol ether / N-arylamide / Alkyl aryl ether / Acetamide / Carboxamide group / Secondary carboxylic acid amide / Ether
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- aromatic ether, acetamides (CHEBI:8050)
Targets
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Enzymes
- 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
- 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:12401364]
- 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:10421611]
- 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. [PubMed:22949628]
- 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. [PubMed:11284709]
- 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. [PubMed:9152599]
- 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
- Flockhart Table of Drug Interactions [Link]
- 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
- 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. [PubMed:8474022]
- 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. [PubMed:10901704]
- 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
- 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. [PubMed:17178771]
- 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
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
- 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
- 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:10421611]
- 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
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
- 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 . [PubMed:10548449]
- 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
- 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:10421611]
- 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
- 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:10421611]
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
- 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:10991954]
- 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:10220563]
Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:52
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