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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
KetajectBristol-Myers Squibb
KetalarParke Davis
KetanestParke Davis
Brand mixturesNot Available
Categories
CAS number6740-88-1
WeightAverage: 237.725
Monoisotopic: 237.092041846
Chemical FormulaC13H16ClNO
InChI KeyYQEZLKZALYSWHR-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
Not Available
6-HydroxyketamineDetails
Ketamine
Not Available
5-HydroxyketamineDetails
Ketamine
Not Available
4-HydroxyketamineDetails
Norketamine
Not Available
4-HydroxynorketamineDetails
Norketamine
Not Available
5-HydroxynorketamineDetails
Norketamine
Not Available
6-HydroxynorketamineDetails
6-Hydroxyketamine
Not Available
6-HydroxynorketamineDetails
5-Hydroxyketamine
Not Available
5-HydroxynorketamineDetails
4-Hydroxyketamine
Not Available
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 point92-93U.S. Patent 3,254,124.
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

Targets

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

4. Delta-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Delta-type opioid receptor P41143 Details

References:

  1. Smith DJ, Pekoe GM, Martin LL, Coalgate B: The interaction of ketamine with the opiate receptor. Life Sci. 1980 Mar 10;26(10):789-95. Pubmed
  2. Hustveit O, Maurset A, Oye I: Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. Pubmed

5. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

References:

  1. Salt PJ, Barnes PK, Beswick FJ: Inhibition of neuronal and extraneuronal uptake of noradrenaline by ketamine in the isolated perfused rat heart. Br J Anaesth. 1979 Sep;51(9):835-8. Pubmed

6. Kappa-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Kappa-type opioid receptor P41145 Details

References:

  1. Smith DJ, Pekoe GM, Martin LL, Coalgate B: The interaction of ketamine with the opiate receptor. Life Sci. 1980 Mar 10;26(10):789-95. Pubmed
  2. Hustveit O, Maurset A, Oye I: Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. Pubmed

7. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. Smith DJ, Pekoe GM, Martin LL, Coalgate B: The interaction of ketamine with the opiate receptor. Life Sci. 1980 Mar 10;26(10):789-95. Pubmed
  2. Hustveit O, Maurset A, Oye I: Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. Pubmed

8. Muscarinic acetylcholine receptor

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details
Muscarinic acetylcholine receptor M2 P08172 Details
Muscarinic acetylcholine receptor M3 P20309 Details
Muscarinic acetylcholine receptor M4 P08173 Details
Muscarinic acetylcholine receptor M5 P08912 Details

References:

  1. Hustveit O, Maurset A, Oye I: Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. Pubmed

9. 5-hydroxytryptamine receptor 2

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details
5-hydroxytryptamine receptor 2B P41595 Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Martin LL, Bouchal RL, Smith DJ: Ketamine inhibits serotonin uptake in vivo. Neuropharmacology. 1982 Feb;21(2):113-8. Pubmed

10. 5-hydroxytryptamine receptor 1

Kind: protein group

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details
5-hydroxytryptamine receptor 1B P28222 Details
5-hydroxytryptamine receptor 1D P28221 Details
5-hydroxytryptamine receptor 1E P28566 Details
5-hydroxytryptamine receptor 1F P30939 Details

References:

  1. Martin LL, Bouchal RL, Smith DJ: Ketamine inhibits serotonin uptake in vivo. Neuropharmacology. 1982 Feb;21(2):113-8. Pubmed

Enzymes

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

Transporters

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

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