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Identification
NameKetobemidone
Accession NumberDB06738
TypeSmall Molecule
GroupsApproved
Description

Ketobemidone is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties. This makes it useful for some types of pain that don’t respond well to other opioids. The most commonly cited equalisation ratio for analgesic doses is 25 mg of ketobemidone hydrobromide to 60 mg of morphine hydrochloride or sulfate and circa 8 mg of ketobemidone by injection.

Structure
Thumb
Synonyms
Cetobemidona
Cetobemidone
Cetobemidonum
Cliradon
Cymidon
Ketobemidone
Ketodur
Ketogan
Ketorax
External Identifiers
  • UNII-PQS1L514CF
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CliradonPfizer
KetoganPfizer
KetoraxPfizer
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ketobemidone hydrochloride
Thumb
  • InChI Key: ALFGKMXHOUSVAD-UHFFFAOYSA-N
  • Monoisotopic Mass: 247.157228921
  • Average Mass: 247.3327
DBSALT000189
Categories
UNIIPQS1L514CF
CAS number469-79-4
WeightAverage: 247.3327
Monoisotopic: 247.157228921
Chemical FormulaC15H21NO2
InChI KeyInChIKey=ALFGKMXHOUSVAD-UHFFFAOYSA-N
InChI
InChI=1S/C15H21NO2/c1-3-14(18)15(7-9-16(2)10-8-15)12-5-4-6-13(17)11-12/h4-6,11,17H,3,7-10H2,1-2H3
IUPAC Name
1-[4-(3-hydroxyphenyl)-1-methylpiperidin-4-yl]propan-1-one
SMILES
CCC(=O)C1(CCN(C)CC1)C1=CC(O)=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPhenylpiperidines
Direct ParentPhenylpiperidines
Alternative Parents
Substituents
  • Phenylpiperidine
  • Aralkylamine
  • Phenol
  • Benzenoid
  • Gamma-aminoketone
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of all types of severe pain, such as postoperative, cancer, kidney stones and fractures.
PharmacodynamicsNot Available
Mechanism of actionKetobemidone (Cliradon, Ketogan, Ketodur, Cymidon, Ketorax, &c.) is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties. This makes it useful for some types of pain that don't respond well to other opioids. The most commonly cited equalisation ratio for analgesic doses is 25 mg of ketobemidone hydrobromide to 60 mg of morphine hydrochloride or sulfate and circa 8 mg of ketobemidone by injection.
Related Articles
Absorption34% (oral), 44% (rectal)
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Ketobemidone is mainly metabolised by conjugation of the phenolic hydroxyl group, and by N-desmethylation. Only about 13-24% is excreted unchanged after iv. administration.

SubstrateEnzymesProduct
Ketobemidone
Reduced ketobemidoneDetails
Ketobemidone
NorketobemidoneDetails
Ketobemidone
Ketobemidone N-oxideDetails
Norketobemidone
Not Available
Dihydroxy norketobemidoneDetails
Ketobemidone
Dihydroxy ketobemidoneDetails
Dihydroxy ketobemidone
Not Available
p-Hydroxymethoxy ketobemidoneDetails
Dihydroxy ketobemidone
Not Available
m-Hydroxymethoxy ketobemidoneDetails
Route of eliminationNot Available
Half lifePlasma half-life: 2.42 +/- 0.41 h (m +/- SD). Elimination half-life: 3.27 +/- 0.32 h
ClearanceNot Available
ToxicityBase: Rat Intravenous LD50: 10 mg/kg; Mouse Intravenous LD50: 14 mg/kg. Hydrochloride salt: Rat Oral LD50: 215 mg/kg; Rat Intravenous LD50: 40 mg/kg
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ketobemidone Action PathwayDrug actionSMP00690
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.996
Blood Brain Barrier+0.9777
Caco-2 permeable+0.7753
P-glycoprotein substrateSubstrate0.8263
P-glycoprotein inhibitor INon-inhibitor0.6758
P-glycoprotein inhibitor IINon-inhibitor0.6722
Renal organic cation transporterInhibitor0.6578
CYP450 2C9 substrateNon-substrate0.8324
CYP450 2D6 substrateSubstrate0.6178
CYP450 3A4 substrateSubstrate0.6483
CYP450 1A2 substrateNon-inhibitor0.8062
CYP450 2C9 inhibitorNon-inhibitor0.889
CYP450 2D6 inhibitorInhibitor0.6678
CYP450 2C19 inhibitorNon-inhibitor0.9396
CYP450 3A4 inhibitorNon-inhibitor0.6532
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9154
Ames testNon AMES toxic0.882
CarcinogenicityNon-carcinogens0.8277
BiodegradationNot ready biodegradable0.9801
Rat acute toxicity2.5982 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6132
hERG inhibition (predictor II)Inhibitor0.6146
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point156.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility3.01 mg/mLALOGPS
logP2.01ALOGPS
logP2.49ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)9.44ChemAxon
pKa (Strongest Basic)8.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity73.12 m3·mol-1ChemAxon
Polarizability28.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Bondesson U, Hartvig P, Danielsson B: Quantitative determination of the urinary excretion of ketobemidone and four of its metabolites after intravenous and oral administration in man. Drug Metab Dispos. 1981 Jul-Aug;9(4):376-80. [PubMed:6114838 ]
  2. Anderson P, Arner S, Bondesson U, Boreus LO, Hartvig P: Clinical pharmacokinetics of ketobemidone. Its bioavailability after rectal administration. Eur J Clin Pharmacol. 1981 Feb;19(3):217-23. [PubMed:7215421 ]
External Links
ATC CodesN02AG02N02AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (83.4 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
References
  1. Kristensen K, Christensen CB, Christrup LL, Nielsen LC: The mu1 and mu2 opioid receptor binding of ketobemidone, norketobemidone and 3-dimethylamino-1,1-diphenylbutene. Pharmacol Toxicol. 1996 Aug;79(2):103-4. [PubMed:8878254 ]
  2. Christensen CB: The opioid receptor binding profiles of ketobemidone and morphine. Pharmacol Toxicol. 1993 Dec;73(6):344-5. [PubMed:8153059 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates th...
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
References
  1. Christensen CB: The opioid receptor binding profiles of ketobemidone and morphine. Pharmacol Toxicol. 1993 Dec;73(6):344-5. [PubMed:8153059 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurot...
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Christensen CB: The opioid receptor binding profiles of ketobemidone and morphine. Pharmacol Toxicol. 1993 Dec;73(6):344-5. [PubMed:8153059 ]
Kind
Protein group
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Voltage-gated cation channel activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
Components:
NameUniProt IDDetails
Glutamate receptor ionotropic, NMDA 1Q05586 Details
Glutamate receptor ionotropic, NMDA 2AQ12879 Details
Glutamate receptor ionotropic, NMDA 2BQ13224 Details
Glutamate receptor ionotropic, NMDA 2CQ14957 Details
Glutamate receptor ionotropic, NMDA 2DO15399 Details
Glutamate receptor ionotropic, NMDA 3AQ8TCU5 Details
Glutamate receptor ionotropic, NMDA 3BO60391 Details
References
  1. Ebert B, Andersen S, Krogsgaard-Larsen P: Ketobemidone, methadone and pethidine are non-competitive N-methyl-D-aspartate (NMDA) antagonists in the rat cortex and spinal cord. Neurosci Lett. 1995 Mar 10;187(3):165-8. [PubMed:7624018 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
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 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, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular Weight:
59940.495 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
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 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 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 ]
Kind
Protein
Organism
Human
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 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 ]
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 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 ]
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Drug created on August 31, 2010 15:02 / Updated on August 17, 2016 12:24