Identification

Name
Ketobemidone
Accession Number
DB06738
Type
Small Molecule
Groups
Experimental
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
External IDs
CIBA 7115 / IDS-NK-001 / IDS-NK-001(SECT.3) / NSC-117863
Product Ingredients
IngredientUNIICASInChI Key
Ketobemidone hydrochlorideU9U6LTV80K5965-49-1HYDFAZFVKRXNJX-UHFFFAOYSA-N
Ketobemidone oxalateNot AvailableNot AvailableOPKJKUCDOASCBQ-UHFFFAOYSA-N
International/Other Brands
Cliradon (Pfizer) / Ketogan (Pfizer) / Ketorax (Pfizer)
Categories
UNII
PQS1L514CF
CAS number
469-79-4
Weight
Average: 247.3327
Monoisotopic: 247.157228921
Chemical Formula
C15H21NO2
InChI Key
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

Pharmacology

Indication

For the treatment of all types of severe pain, such as postoperative, cancer, kidney stones and fractures.

Pharmacodynamics
Not Available
Mechanism of action

Ketobemidone (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.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
AKappa-type opioid receptor
agonist
Human
ADelta-type opioid receptor
agonist
Human
UNMDA receptor
antagonist
Human
Absorption

34% (oral), 44% (rectal)

Volume of distribution
Not Available
Protein binding
Not 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.

Route of elimination
Not Available
Half life

Plasma half-life: 2.42 +/- 0.41 h (m +/- SD). Elimination half-life: 3.27 +/- 0.32 h

Clearance
Not Available
Toxicity

Base: 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
PathwayCategory
Ketobemidone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Ketobemidone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Ketobemidone.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Ketobemidone.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Ketobemidone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Ketobemidone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Ketobemidone.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Ketobemidone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ketobemidone.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Ketobemidone.
5-androstenedioneThe metabolism of Ketobemidone can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

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
Human Metabolome Database
HMDB0041913
KEGG Drug
D08100
KEGG Compound
C11792
PubChem Compound
10101
PubChem Substance
175427088
ChemSpider
9697
BindingDB
50045604
ChEBI
6125
ChEMBL
CHEMBL47072
Wikipedia
Ketobemidone
ATC Codes
N02AG02 — Ketobemidone and antispasmodicsN02AB01 — Ketobemidone
MSDS
Download (83.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentInguinal Hernias / Postoperative pain1

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)156.5 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Phenylpiperidines
Direct Parent
Phenylpiperidines
Alternative Parents
Aralkylamines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Gamma-amino ketones / Benzene and substituted derivatives / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Phenylpiperidine / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Aralkylamine / Monocyclic benzene moiety / Gamma-aminoketone / Benzenoid / Ketone / Tertiary amine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines (CHEBI:6125)

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...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
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 synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
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 n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
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 p...

Components:
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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
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]
  3. Yasar U, Annas A, Svensson JO, Lazorova L, Artursson P, Al-Shurbaji A: Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P-glycoprotein. Xenobiotica. 2005 Aug;35(8):785-96. doi: 10.1080/00498250500183181 . [PubMed:16278191]
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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 trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
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]
  2. Yasar U, Annas A, Svensson JO, Lazorova L, Artursson P, Al-Shurbaji A: Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P-glycoprotein. Xenobiotica. 2005 Aug;35(8):785-96. doi: 10.1080/00498250500183181 . [PubMed:16278191]
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
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]
  2. Yasar U, Annas A, Svensson JO, Lazorova L, Artursson P, Al-Shurbaji A: Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P-glycoprotein. Xenobiotica. 2005 Aug;35(8):785-96. doi: 10.1080/00498250500183181 . [PubMed:16278191]

Drug created on August 31, 2010 15:02 / Updated on November 02, 2018 09:16