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Identification
NameKetamine
Accession NumberDB01221  (APRD00493)
Typesmall molecule
Groupsapproved
Description

A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, N-methyl-D-aspartate) and may interact with sigma receptors. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(±)-ketamineNot AvailableNot Available
2-(2-Chloro-phenyl)-2-methylamino-cyclohexanoneNot AvailableNot Available
2-(methylamino)-2-(2-chlorophenyl)cyclohexanoneNot AvailableNot Available
2-(o-chlorophenyl)-2-(methylamino)-cyclohexanoneNot AvailableNot Available
DL-ketamineNot AvailableNot Available
NMDANot AvailableNot Available
Salts
Name/CAS Structure Properties
Ketamine hydrochloride
1867-66-9
Thumb
  • InChI Key: VCMGMSHEPQENPE-UHFFFAOYNA-N
  • Monoisotopic Mass: 273.068719585
  • Average Mass: 274.186
DBSALT000396
Brand names
NameCompany
KetajectNot Available
KetalarNot Available
KetanestNot Available
KetolarNot Available
Brand mixturesNot Available
Categories
CAS number6740-88-1
WeightAverage: 237.725
Monoisotopic: 237.092041846
Chemical FormulaC13H16ClNO
InChI KeyInChIKey=YQEZLKZALYSWHR-UHFFFAOYSA-N
InChI
InChI=1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3
IUPAC Name
2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one
SMILES
CNC1(CCCCC1=O)C1=CC=CC=C1Cl
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassHalobenzenes
Direct parentChlorobenzenes
Alternative parentsCyclohexanones; Aryl Chlorides; Dialkylamines; Polyamines; Organochlorides
Substituentsaryl chloride; aryl halide; ketone; secondary aliphatic amine; polyamine; secondary amine; organochloride; organohalogen; carbonyl group; amine; organonitrogen compound
Classification descriptionThis compound belongs to the chlorobenzenes. These are compounds containing one or more chlorine atoms attached to a benzene moiety.
Pharmacology
IndicationFor use as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation.
PharmacodynamicsKetamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression. Ketamine is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. The anesthetic state produced by Ketamine has been termed “dissociative anesthesia” in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticularactivating and limbic systems).
Mechanism of actionKetamine has several clinically useful properties, including analgesia and less cardiorespiratory depressant effects than other anaesthetic agents, it also causes some stimulation of the cardiocascular system. Ketamine has been reported to produce general as well as local anaesthesia. It interacts with N-methyl-D-aspartate (NMDA) receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Unlike other general anaesthetic agents, ketamine does not interact with GABA receptors.
AbsorptionRapidly absorbed following parenteral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

SubstrateEnzymesProduct
Ketamine
NorketamineDetails
Ketamine
    6-HydroxyketamineDetails
    Ketamine
      5-HydroxyketamineDetails
      Ketamine
        4-HydroxyketamineDetails
        Norketamine
          4-HydroxynorketamineDetails
          Norketamine
            5-HydroxynorketamineDetails
            Norketamine
              6-HydroxynorketamineDetails
              6-Hydroxyketamine
                6-HydroxynorketamineDetails
                5-Hydroxyketamine
                  5-HydroxynorketamineDetails
                  4-Hydroxyketamine
                    4-HydroxynorketamineDetails
                    Route of eliminationNot Available
                    Half life2.5-3 hours.
                    ClearanceNot Available
                    ToxicityNot Available
                    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 + 0.9974
                    Blood Brain Barrier + 0.9826
                    Caco-2 permeable + 0.6326
                    P-glycoprotein substrate Substrate 0.5753
                    P-glycoprotein inhibitor I Non-inhibitor 0.5948
                    P-glycoprotein inhibitor II Non-inhibitor 0.8383
                    Renal organic cation transporter Non-inhibitor 0.6737
                    CYP450 2C9 substrate Non-substrate 0.6363
                    CYP450 2D6 substrate Substrate 0.8918
                    CYP450 3A4 substrate Substrate 0.7407
                    CYP450 1A2 substrate Non-inhibitor 0.7323
                    CYP450 2C9 substrate Non-inhibitor 0.7985
                    CYP450 2D6 substrate Non-inhibitor 0.6912
                    CYP450 2C19 substrate Non-inhibitor 0.5347
                    CYP450 3A4 substrate Non-inhibitor 0.8253
                    CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5426
                    Ames test Non AMES toxic 0.7223
                    Carcinogenicity Non-carcinogens 0.8878
                    Biodegradation Not ready biodegradable 0.9937
                    Rat acute toxicity 2.3939 LD50, mol/kg Not applicable
                    hERG inhibition (predictor I) Weak inhibitor 0.8859
                    hERG inhibition (predictor II) Inhibitor 0.6047
                    Pharmacoeconomics
                    Manufacturers
                    • Jhp pharmaceuticals llc
                    • Bedford laboratories div ben venue laboratories inc
                    • Bioniche pharma usa llc
                    • Hospira inc
                    Packagers
                    Dosage forms
                    FormRouteStrength
                    SolutionIntravenous
                    Prices
                    Unit descriptionCostUnit
                    Ketamine hcl powder7.22USDg
                    Ketamine hcl-ns 50 mg/5 ml syr2.82USDml
                    Ketamine 100 mg/ml vial2.36USDml
                    Ketalar 100 mg/ml vial1.95USDml
                    Ketamine hcl-ns 100 mg/10 ml1.95USDml
                    Ketamine HCl 50 mg/ml Solution1.77USDml
                    Ketalar 10 mg/ml vial0.99USDml
                    Ketamine 10 mg/ml vial0.99USDml
                    Ketalar 50 mg/ml vial0.75USDml
                    Ketamine 50 mg/ml vial0.61USDml
                    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
                    PatentsNot Available
                    Properties
                    Statesolid
                    Experimental Properties
                    PropertyValueSource
                    melting point92.5 °CPhysProp
                    logP2.9Not Available
                    Predicted Properties
                    PropertyValueSource
                    water solubility4.64e-02 g/lALOGPS
                    logP2.69ALOGPS
                    logP3.35ChemAxon
                    logS-3.7ALOGPS
                    pKa (strongest acidic)18.78ChemAxon
                    pKa (strongest basic)7.45ChemAxon
                    physiological charge1ChemAxon
                    hydrogen acceptor count2ChemAxon
                    hydrogen donor count1ChemAxon
                    polar surface area29.1ChemAxon
                    rotatable bond count2ChemAxon
                    refractivity65.55ChemAxon
                    polarizability24.97ChemAxon
                    number of rings2ChemAxon
                    bioavailability1ChemAxon
                    rule of fiveYesChemAxon
                    Ghose filterYesChemAxon
                    Veber's ruleYesChemAxon
                    MDDR-like ruleNoChemAxon
                    Spectra
                    SpectraNot Available
                    References
                    Synthesis Reference

                    John A. Flores, Kenton L. Crowley, “Process for the preparation of ketamine ointment.” U.S. Patent US5817699, issued June, 1995.

                    US5817699
                    General Reference
                    1. Harrison NL, Simmonds MA: Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol. 1985 Feb;84(2):381-91. Pubmed
                    2. Bergman SA: Ketamine: review of its pharmacology and its use in pediatric anesthesia. Anesth Prog. 1999 Winter;46(1):10-20. Pubmed
                    3. Bonanno FG: Ketamine in war/tropical surgery (a final tribute to the racemic mixture). Injury. 2002 May;33(4):323-7. Pubmed
                    4. Lankenau SE, Sanders B, Bloom JJ, Hathazi D, Alarcon E, Tortu S, Clatts MC: First injection of ketamine among young injection drug users (IDUs) in three U.S. cities. Drug Alcohol Depend. 2007 Mar 16;87(2-3):183-93. Epub 2006 Sep 18. Pubmed
                    5. Reboso Morales JA, Gonzalez Miranda F: [Ketamine] Rev Esp Anestesiol Reanim. 1999 Mar;46(3):111-22. Pubmed
                    External Links
                    ResourceLink
                    KEGG DrugD08098
                    KEGG CompoundC07525
                    PubChem Compound3821
                    PubChem Substance46508295
                    ChemSpider3689
                    BindingDB50044140
                    ChEBI6121
                    ChEMBLCHEMBL742
                    Therapeutic Targets DatabaseDAP001148
                    PharmGKBPA450144
                    Drug Product Database2246796
                    RxListhttp://www.rxlist.com/cgi/generic3/ketamine.htm
                    Drugs.comhttp://www.drugs.com/cdi/ketamine.html
                    WikipediaKetamine
                    ATC CodesN01AX03N01AX14
                    AHFS Codes
                    • 28:04.00
                    • 28:04.92
                    PDB EntriesNot Available
                    FDA labelNot Available
                    MSDSshow(67.5 KB)
                    Interactions
                    Drug Interactions
                    Drug
                    MemantineIncreased risk of CNS adverse effects with this association
                    TelithromycinTelithromycin may reduce clearance of Ketamine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Ketamine if Telithromycin is initiated, discontinued or dose changed.
                    ThiotepaThiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Ketamine, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Ketamine if Thiotepa is initiated, discontinued or dose changed.
                    TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Ketamine. Consider alternate therapy or monitor for changes in Ketamine therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
                    VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ketamine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of ketamine if voriconazole is initiated, discontinued or dose changed.
                    Food InteractionsNot Available

                    1. Glutamate receptor ionotropic, NMDA 3A

                    Kind: protein

                    Organism: Human

                    Pharmacological action: yes

                    Actions: antagonist

                    Components

                    Name UniProt ID Details
                    Glutamate receptor ionotropic, NMDA 3A Q8TCU5 Details

                    References:

                    1. Smothers CT, Woodward JJ: Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits. J Pharmacol Exp Ther. 2007 Aug;322(2):739-48. Epub 2007 May 14. Pubmed
                    2. Harrison NL, Simmonds MA: Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol. 1985 Feb;84(2):381-91. Pubmed
                    3. Sinner B, Graf BM: Ketamine. Handb Exp Pharmacol. 2008;(182):313-33. Pubmed
                    4. Radovanovic D, Pjevic M: [Ketamine: the past 30 years and its future] Med Pregl. 2003 Sep-Oct;56(9-10):439-45. Pubmed

                    2. Substance-P receptor

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: antagonist

                    Components

                    Name UniProt ID Details
                    Substance-P receptor P25103 Details

                    References:

                    1. Okamoto T, Minami K, Uezono Y, Ogata J, Shiraishi M, Shigematsu A, Ueta Y: The inhibitory effects of ketamine and pentobarbital on substance p receptors expressed in Xenopus oocytes. Anesth Analg. 2003 Jul;97(1):104-10, table of contents. Pubmed

                    3. D(2) dopamine receptor

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: agonist partial agonist

                    Components

                    Name UniProt ID Details
                    D(2) dopamine receptor P14416 Details

                    References:

                    1. Seeman P, Guan HC, Hirbec H: Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Synapse. 2009 Aug;63(8):698-704. Pubmed

                    1. Cytochrome P450 2C9

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: substrate

                    Components

                    Name UniProt ID Details
                    Cytochrome P450 2C9 P11712 Details

                    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
                    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

                    2. Cytochrome P450 3A4

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: substrate

                    Components

                    Name UniProt ID Details
                    Cytochrome P450 3A4 P08684 Details

                    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
                    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 2B6

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: substrate

                    Components

                    Name UniProt ID Details
                    Cytochrome P450 2B6 P20813 Details

                    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
                    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

                    4. Prostaglandin G/H synthase 1

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: substrate

                    Components

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

                    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

                    5. Cytochrome P450 2C8

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: substrate

                    Components

                    Name UniProt ID Details
                    Cytochrome P450 2C8 P10632 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

                    1. Multidrug resistance protein 1

                    Kind: protein

                    Organism: Human

                    Pharmacological action: unknown

                    Actions: inhibitor

                    Components

                    Name UniProt ID Details
                    Multidrug resistance protein 1 P08183 Details

                    References:

                    1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed

                    Comments
                    Drug created on June 13, 2005 07:24 / Updated on March 03, 2014 21:13